6^th World Congress on Cell & Stem Cell Research February 29-March 02, 2016 Philadelphia, Pennsylvania, USA

Biography:

Brian Mehling, M.D., M.S. is a practicing American orthopedic trauma surgeon, researcher, and philanthropist. Dr. Mehling started his path in medicine through undergraduate study at Harvard University, obtaining his Bachelor of Arts and Master of Science degrees in Biochemistry from Ohio State University. Completing his degree of medicine at Wright State University School of Medicine, Dr. Mehling received post graduate education through residencies and fellowships at St. Joseph’s Hospital in Paterson, NJ and the Graduate Hospital in Philadelphia, PA. Dr. Mehling operates his own practice, Mehling Orthopedics, in both West Islip, NY and Hackensack. NJ.

Abstract:

BHI Therapeutic Sciences, LLC is a healthcare research and consulting company, dedicated to the development of stem cell therapies. Our scientific and medical teams are focused on IRB-approved protocols, designed to measure the safety and efficacy of intravenous, intra-articular, and intrathecal stem cell treatments. The purpose of our study is primarily to monitor the immune response in order to validate the safety of intravenous infusion of human umbilical cord blood derived MSCs (UC-MSCs), and secondly, to evaluate effects on biomarkers associated with chronic inflammation. Twenty patients were treated for conditions associated with chronic inflammation and for the purpose of anti-aging. They have been given one intravenous infusion of UC-MSCs. Our study of blood test markers of 20 patients with chronic inflammation before and within three months after MSCs treatment demonstrates that there is no significant changes and MSCs treatment was safe for the patients. Analysis of different indicators of chronic inflammation and aging included in initial, 24-hours, two weeks and three months protocols showed that stem cell treatment was safe for the patients; there were no adverse reactions. Moreover data from follow up protocols demonstrates significant improvement in energy level, hair, nails growth and skin conditions. Intravenously administered UC-MSCs were safe and effective in the improvement of symptoms related to chronic inflammation. Further close monitoring and inclusion of more patients are necessary to fully characterize the advantages of UC-MSCs application in treatment of symptoms related to chronic inflammation

Biography:

Lewis Clarke obtained his Master of Science from University of Texas at Dallas in 1977 in Human Development with Biostatistics. In 1986, he completed his Doctor of Medicine degree from Texas Tech School of Medicine. In 1987, he received his Ph.D. from the Department of Cell Biology and Neurobiology at University of Texas Health Sciences Center at Dallas. He completed his medical internship at Emory University and Baylor College of Medicine in 1986 and finished his residency training at Baylor College of Medicine in Physical Medicine and Rehabilitation. He has a clinical and research practice in the Houston Texas area and has started two rehabilitation hospitals.

Abstract:

Intrinsic mechanisms of neuronal repair in the central nervous system through neuroregenerative processes have previously been presented. Similar biochemical and neurochemical mechanisms exist which are known to be neuroprotective. Exploiting and augmenting these intrinsic processes could minimize or mitigate neuronal damage in acute brain and spinal cord injuries resulting from stroke or trauma. The inflammatory response together with the oxidative stress of the acute injury represent the most likely therapeutic targets for intervention. Similarly, in chronic, progressive neurodegenerative disorders resulting from repetitive cumulative minimally-traumatic injuries such as concussion and subsequent chronic trauma encephalopathies (CTE), persistent or chronic neuroinflammation and the products of oxidative stress responses could account for the observed brain pathologies. The multiple pathologies present in various combinations in all neurodegenerative disorders include β-amyloid and amyloid plaques, hyperphosphorylated tau protein, neurofibrillary tangles, and microglial activation. It is now understood that within the CNS there exists a protective and anti-inflammatory neurochemistry many components of which can also promote neurogenesis and functional as well as structural restoration. It is intuitive that given the numerous interdependent and symbiotic systems involved in the preservation of the integrity and function of the brain, no single intervention or therapy is likely. A logical beginning would be to increase antioxidant gene expression and the scavenging of free radicals, suppressing or blocking the NMDA receptor to decrease glutamate and aspartate-induced cytotoxicity, inhibiting pro-inflammatory cytokines and metalloproteinases, enhancing anti-inflammatory cytokines, and suppressing activation of microglia. The augmentation of mitochondrial number and energy production is DNA protective and would address all cellular function including stem cell production, migration, and differentiation. Much is now known about the contribution of CoQ10, carnitine, lipoic acid, and pyrroloquinoline quinone in this regard. An integrative approach should include bioactive lipids in the mitochondrial membrane, eicosanoid modulating PUFA’s, sigma 1 receptors, and neurosteroids produced de novo in the glia. These are also catalysts and promote neurogenesis and neurite outgrowth through their activation of sigma 1 receptors in the mitochondrial membrane lipid rafts of the endoplasmic reticulum. Activated sigma 1 receptors increase calcium in the mitochondria resulting in activation of the TCA cycle, increasing mitochondrial hypermetabolism ultimately resulting in neurite outgrowth as well as neuroprotection. Neurodegenerative processes are multifactorial in etiology. Controlling inflammatory reactions and preventing their chronicity and curtailing oxidative and cytotoxic effects of acute neurologic injuries would be neuroprotective in the acute phase and avert the chronic encephalopathies. These same neuroprotective mechanisms are also neuroregenerative.

Biography:

Shanmugasundaram Ganapathy-Kanniappan obtained his Ph.D degree from the University of Madras and underwent postdoctoral training at premier institutes such as National Institute of Immunology (NII), New Delhi, University of California at Los Angeles (UCLA) and Johns Hopkins University. Currently, he is an assistant professor at the Johns Hopkins University School of Medicine. He has several publications in reputed journals and has written many reviews and a book chapter on cancer metabolism and therapeutic opportunities.

Abstract:

Cancer-related high mortality rate and poor prognosis are often attributed to metastasis, the process of dissemination of cancer cells to distal organs from the primary site of origin. Further metastatic cancers are often known to be refractory to therapies. Development of an effective therapeutic strategy for metastatic cancer relies on the identification of sensitive molecular targets that are specific and critical for the growth and propagation of metastatic cells. However, tumor heterogeneity impedes the complete understanding of the metastatic proclivity any solid malignancy and the elucidation of potential therapeutic target. Further, the complexity of metastatic process [which involves sequential steps like dissociation of cancer cells from the site of origin, transport in the circulation, and final sequestration into distal organs] also confound the identification of any sensitive target or pathway. Recently, we reported an algorithm of matrigel-free, anchorage independent growth condition to select and isolate “metastatic potential” cells from heterogeneous population of cancer cells. Our preliminary data show that these early-stage metastatic cancer cells undergo a metabolic reprogram to facilitate growth and development. More importantly, such metabolic reprogramming involves upregulation of cancer-stem cell markers. Emerging reports indicate cancer-stem cell markers affect energy metabolism in cancer cells. Together, we show that metabolic reprogramming and metastatic potential of cancer cells are correlated with the expression of one or more cancer-stem cell markers. Thus, cancer stem cell markers remain as attractive target for therapeutic interference with cancer metabolism as well as metastasis.

Biography:

Nirmala Mavila, completed her PhD in Biotechnology from Mysore University, India. She completed her postdoctoral trainings at Purdue University and Children’s Hospital Los Angeles before joining as a faculty at Cedars-Sinai Medical Center, Los Angeles, CA. Her main research interest is progenitor/stem cells in liver development, regeneration and diseases.

Abstract:

Prominin1 (PROM1, CD133) is a penta-transmembrane glycoprotein known to express in various kinds of progenitor cells. It was originally discovered as a hematopoietic stem cell marker. Its expression is restricted to the plasma membrane protrusions and has been identified as a cholesterol binding protein. However its function yet to be identified. Studies have demonstrated that PROM1 positive tumor initiating cells form more aggressive tumors in xenograft models compared to PROM1 negative cancer cells. Its expression found to be correlated with poor prognosis of various cancers. It is believed that PROM1 maintains the stem cell-ness of progenitor cells and losses its expression during cellular differentiation. Our recent studies have demonstrated that murine embryonic liver progenitor cells or hepatoblasts expresses PROM1 as early as embryonic stage E11 and reduces its expression as the liver develops into a mature organ. Our studies also have demonstrated that Fibroblast growth factor receptor 2 mediated activation of AKT-beta-catenin signaling, plays an important role in the proliferation of PROM1 positive hepatoblasts and liver cancer stem cells in vitro. Importantly, our recent studies have demonstrated an increased expression of PROM1 in cholestatic liver diseases. However its pathological significance is yet to be discovered.

Biography:

Lucie Bacakova, MD, PhD, Assoc. Prof. has graduated from the Faculty of General Medicine, Charles University, Prague, Czechoslovakia in 1984. She has completed her Ph.D at the age of 32 years from the Czechoslovak Academy of Sciences, and became Associated Professor at the 2nd Medical Faculty, Charles University. She is the Head of the Department of Biomaterials and Tissue Engineering, Institute of Physiology, Academy of Sciences of the Czech Republic. She is a specialist for studies on cell-material interaction and vascular, bone and skin tissue engineering. She has published more than 150 papers in reputed journals (h-index 26).

Abstract:

Adipose-derived stem cells (ASCs) are promising for engineering of various tissues, such as bone, cartilage, blood vessels, heart, skeletal muscle, neural tissue, skin, liver or pancreatic islet cells. ASCs have been already clinically applied for cell-assisted lipotransfer for tissue augmentation, for healing the wound after radiation therapy and for skin rejuvenation. Due to their immunosuppressive and immunomodulatory function, ASCs have been clinically tested and applied for treatment of inflammatory and autoimmune diseases. The adipose tissue can be obtained by a relative non-invasive method, i.e. liposuction. The quality and quantity of isolated ASCs can be influenced by parameters of liposuction, such as the type of anesthesia, composition of the tumescent solution, and particularly the amount of negative pressure. In this study, we focused on ASCs isolated from lipoaspirates taken from the same patient (a 43-year-old woman) under low negative pressure (-200 mmHg, LP) or high negative pressure (-700 mm Hg, HP). The number of isolated ASCs and their subsequent proliferation activity in vitro was higher in cells obtained under HP. These differences persisted in passaged cells (tested up to 3 passages), and also after cryopreservation of cells. However, when confluent ASCs were exposed to an osteogenic medium for 5 days, the osteogenic cell differentiation, measured by intensity of fluorescence of collagen I, alkaline phosphatase and osteocalcin, was more pronounced in cells obtained under LP. Thus, ASCs obtained under both pressures have specific advantages, and their choice depends on their application, i.e. if their rapid growth or early osteogenic differentiation is required.

Biography:

Jian Zhou is a scientist and researcher,currently working in Beijing Stomatological Hospital, China.His research intersted areas are stem cell,regenarative medicine,odontoblastspecification and dentin regeneration.

Abstract:

New endodontic therapies that attempt to regenerate dental pulp and dentin may provide alternative solutions to traditional procedures. Previously, we have reported that odontogenesis factors, BMP7 and Wnt10a are highly expressed by odontoblasts. Consistently, BMP and canonical Wnt signaling pathways synergistically promote odontogenesis in vitro. To examine Wnt and BMP mediated dental pulp regeneration, we delivered the two factors into endodontically treated porcine incisors. The regenerated dental pulp and dentin were assessed by histological analysis, micro-CT, scanning electronic microscope (SEM), and hardness tests by nanoindentation. The present study aimed to: 1) quantify the regenerated dentin using histological analysis and micro-CT; 2) measure mechanical parameters of regenerated dentin; 3) assess the microstruture of the regenerated dentin by scanning electronic microscope (SEM).We regenerated dentin and dental pulp in endodontically treated teeth by homing and inducing endogenous perioapical cell migration and differentiation into dental pulp cells. Our results demonstrate that the two factors induce dentin regeneration and that the mechanical character and mineral density of regenerated dentin is comparable to the native dentin. This research supports a new approach to endodontic therapy as regenerative pulp and dentin have been shown to function like the native tooth.

Biography:

Wen-Chi, Yang has completed her MD at the age of 25 years from Kaohsiung medical university and completed her Ph.D at the age of 38 years from the same university. She had 2 years postdoctoral studies from Harvard Medical School during 2007 to 2009 and half year postdoctoral studies from Massachusetts Institute of Technology after then. She is hematology, medical oncology and hospice care specialist in Taiwan. She is the attending physician of Yuan’s general hospital. She is also chief stuff of molecular medicine lab in Yuan’s general hospital.

Abstract:

Anemia is a common condition in the older population. Unexplained anemia (UA) contributes one third of anemia in older ages. And most of those patients can meet at least one of the diagnosis criteria of myelodysplastic syndrome (MDS). In MDS, leukemia transformation is a lethal problem. Many genes alternations and clinical characteristics have been reported to associate with leukemia transformation in MDS patients. Iron overload is one majority causes. Siderophores help transport iron. Type 2-hydroxybutyrate dehydrogenase (BDH2) is a rate-limiting factor in the biogenesis of siderophores. We analyzed 187 MDS patients, compared with de novo acute myeloid leukemia patients and normal bone marrow patients. Elevated BDH2mRNA expression was observed in MDS patient bone marrow (P=0.009) and was related to ferritin levels (P=0.049). The higher BDH2 expression (15%) group showed a greater risk for leukemia transformation than the lower expression group (3.18%) (P=0.017). We investigated the mechanism by using RNA-interference–mediated-knockdown of BDH2 (BDH2-KD) in the leukemia cell line, THP1. Cell cycle arrest and increasing apoptosis rate by surviving were noticed in BDH2-KD cells. Here we present a novel predictor of leukemia transformation in MDS, that relates to iron metabolism, apoptosis and cell cycle control.

Biography:

John A. Barrett has completed his Ph.D. from Saint Johns University, NY. He is presently Vice President of R & D and head of translational research at Ziopharm Oncology with a research focus in immunotherapy, oncology, targeted radiopharmaceuticals and biomarkers. During his career he was responsible for numerous INDs and NDAs and has authored 45 papers in peer review journals.

Abstract:

Immunotherapy has been shown to be effective in breast cancer patients. In breast cancer, CD8+ T-cells, are activated by IL-12, have been shown to correlate with anti-tumor activity and prolonged survival. Ad-RTS-IL-12 (Ad) is a replication-incompetent adenovirus engineered to express IL-12, via our RheoSwitch Therapeutic System® gene switch. When injected directly into a tumor. IL-12 expression is off devoid of the activator ligand, veledimex (V), while IL-12 production is turned on in a dose-dependent manner by V p.o. Mechanistic studies in the 4T1 syngeneic mouse breast tumor model with Ad+V have shown a dose-related increase in tumor IL-12 mRNA and IL-12 protein expression. Cessation of V resulted in a return to baseline IL-12 mRNA and IL-12 protein expression. These changes correlated with a local and systemic immune and anti-tumor response. Low dose chemotherapy primes the immune system and in combination with immunotherapy may augment tumor specific T-cells resulting in enhanced efficacy. In the 4T1 mouse mammary tumor model Ad (1e10vp)+V (30 mg/m2) with low dose chemotherapy significantly inhibited tumor growth in a supra-additive fashion concomitant with increased median survival vs. single agent alone. Based on these results an open label, phase 2 trial evaluating the safety of inducible IL-12 expression in heavily pretreated subjects with recurrent/metastatic breast cancer was performed. In this study, treatment with Ad+V resulted in increase in IL-12, downstream IFNg followed by rapid increase in IL-10 and IP-10. In the 12 subjects administrated Ad+ V there was a total of 16 non-injected evaluable lesions in 7 subjects. Of the 16 lesions, 1 lesion had decrease in lesion diameter ranging from 10- 19%, 2 lesions 30-49%, and 3 lesions 50-100%. Most common ≥ Grade 3 treatment emergent adverse events in BC and melanoma included neutropenia and hyponatremia (16% each), hypotension, cytokine release syndrome, AST increase (11% each), dehydration, fatigue, pyrexia (8% each). All TEAEs and SAEs ≥ Grade 3 reversed rapidly upon discontinuation of veledimex The results of this study showed biologic activity with an acceptable therapeutic index. In summary, Ad+V is a novel gene therapy which controls local expression of IL-12, which may result in the collapse of tumor stroma and stimulating an anti-cancer T cell immune response. The ability to regulate the production of IL-12 by modulating V dosing may result in an improved therapeutic index in combination with standard of care.

Biography:

Anderson completed her PhD at the University of Manchester, UK in the Faculty of Medicine. She is the Established Chair in Biomedical Sciences at the University of Bradford. She has published more than 450 papers, 8 books, successfully supervised 30 PhD students, has an Hirsch factor of 51. She is Editor –in- Chief of a Book Series for the Royal Society of Chemistry and is Consultant to many International Organisations, such as the World Health Organisation/ International Programme of Chemical Safety. She is/ has been member of the editorial Board of ten international journals.

Abstract:

Nanotechnology has preceded nanotoxicology and little is known of the effects of nanoparticles in human systems, let alone in diseased individuals. Therefore, the effects of titanium dioxide (TiO2) nanoparticles in peripheral blood lymphocytes from patients with respiratory diseases [lung cancer, chronic obstructive pulmonary disease (COPD) and asthma] were compared with those in healthy Individuals, to determine differences in sensitivity to nanochemical insult. The Comet assay was performed according to recommended guidelines. The micronucleus assay and ras oncoprotein detection were conducted according to published standard methods. The results showed statistically significant concentration-dependent genotoxic effects of TiO2 NPs in both respiratory patient and control groups in the Comet assay. The TiO2 NPs caused DNA damage in a concentration dependent manner in both groups (respiratory and healthy controls) with the exception of the lowest TiO2 concentration (10 µg/ml) which did not induce significant damage in healthy controls (ns). When OTM data were used to compare the whole patient group and the control group, the patient group had more DNA damage (p > 0.001) with the exception of 10 µg/ml of TiO2 that caused less significant damage to patient lymphocytes (p < 0.05). Similarly, there was an increase in the pattern of cytogenetic damage measured in the MN assay without statistical significance except when compared to the negative control of healthy individuals. Furthermore, when modulation of ras p21 expression was investigated, regardless of TiO2 treatment, only lung cancer and COPD patients expressed measurable ras p21 levels. All results were achieved in the absence of cytotoxicity.

Biography:

Qing Ma has completed her Ph.D. in 1990 from Thomas Jefferson University and subsequently postdoctoral studies at Harvard Medical School. She is currently associate professor of Cancer Medicine at UT M.D. Anderson Cancer Center.

Abstract:

Graft-verses-host disease (GVHD) is a major complication in allogeneic bone marrow transplantation, and characterized by epithelial cell injury in skin, intestine and liver. The development of GVHD involves donor T cell activation including proliferation, differentiation and inflammatory cytokine production, which lead to specific tissue damage. The interactions between the complement system and lymphocytes have been shown to regulate alloreactive T cell and APC function in the setting of allograft rejection. In recently published studies, we demonstrated that reduced GVHD mortality/morbidity in C3-deficient mice is associated with a decrease in donor Th1/Th17 polarization and Th1-driven DC activation. The number of donor-derived T cells including IFNγ+, IL17+ and IL17+IFNγ+ subsets was decreased in secondary lymphoid organs of C3-/- recipients. We conclude that C3 regulates Th1/17 differentiation in BMT, and define a novel function of the complement system in GVHD. To investigate whether anti-complement therapy has any impact on human T cell activation, a drug candidate Compstatin was used to inhibit C3 activation in this study. We found the frequency of IFN-γ (Th1), IL-4 (Th2), IL-17 (Th17), IL-2 and TNF-α producing cells were significantly reduced among activated CD4+ cells in the presence of Compstatin. Compstatin treatment decreased the proliferation of both CD4+ and CD8+ T cells upon TCR stimulation. We examined complement deposition in the skin and lip biopsy samples of patients diagnosed with cutaneous GVHD. C3 deposition was detected in the squamous epithelium and dermis, blood vessels and damaged sweat glands, and associated with gland damage and regeneration. We conclude that C3 mediates Th1/Th17 polarization in human T cell activation and skin GVHD in patients.

Biography:

Dinulescu is an Assistant Professor at Harvard Medical School. She received her Ph.D. from Oregon Health and Science University and completed her postdoctoral studies in the field of Cancer Genetics at MIT. Dr. Dinulescu’s research interests focus on cancer biology, malignancies of the gonads and reproductive tract, with a special emphasis on ovarian cancer research and endometriosis. Our laboratory is actively investigating the key contribution of cancer stem cells (CSCs) to tumor chemoresistance. Our current studies focus on better understanding the mechanism of stem cell signaling in the maintenance of the CSC niche and ovarian tumorigenesis. The aim is to harness the power of nanotechnology to develop improved “homing” technologies for the delivery of therapeutic agents specifically targeting and sensitizing ovarian cancer cells, including CSCs, in a spatio-temporal fashion.

Abstract:

Cancer stem cells (CSCs) are considered to be important for tumor development, metastasis, and chemoresistance based on their key ability to survive standard cancer chemotherapies. Multiple studies have now defined CSCs as having an increased tumorigenic ability in serial transplantation experiments conducted in tumor xenografts. This assay, however, may not be entirely accurate in clearly identifying CSCs. Nevertheless, there is enough evidence to support the idea that CSCs are necessary to initiate and propagate tumor diversity. In addition, CSCs are studied in multiple solid tumors, including ovarian cancer, due to their intrinsic chemoresistance properties. Thus, while non-CSCs have been shown to be sensitive to available therapies, CSCs are enriched in response to treatment and regenerate an increasingly platinum resistant tumor. Furthermore, similar to normal stem cells, CSCs are likely shielded from damage and injury by the tumor niche microenvironment, which makes it difficult to target them therapeutically. The cellular origin of ovarian cancer stem cells has been difficult to identify. Multiple stem cell models have been proposed. One model proposes that CSCs can originate either from somatic adult stem cells or from progenitor non-stem cells. The ovarian surface epithelium and distal fallopian tube, which are tumor initiation sites, consist of both adult stem cells and also progenitor cells that are relatively undifferentiated and capable of differentiating into distinct morphological subtypes. We have recently found that ovarian cancer and somatic stem cells share common molecular pathways and markers, which is consistent with the model that some cancer stem cells may either arise from adult stem cells or most likely evolve to mimic somatic stem cell properties.

Biography:

Thomas Bartosh completed his PhD degree in Cell Biology and Genetics from The University of North Texas HSC. He joined the Institute for Regenerative Medicine (IRM) at Texas A&M University in 2008 to develop therapies with mesenchymal stem cells (MSCs). Currently, he an Assistant Professor of Internal Medicine and Director of flow cytometry and microscopy at the IRM. He studies the advantages of using three-dimensional (3-D) culture methods to activate MSCs and exploit their inherent therapeutic potential. This approach was pioneered by Dr. Bartosh at the IRM and has been highlighted in numerous publications.

Abstract:

Mesenchymal stem cells (MSCs) have many potential applications in cancer therapy. In particular, there is interest in exploiting the notable tumor-tropic properties of MSCs to deliver anti-cancer factors directly into tumors. Previously we reported that when MSCs are prepared as spheroids in 3-D hanging drop cultures, expression of tumor-suppressive factors (TRAIL, IL-24, CD82) was augmented and MSC size was effectively reduced resulting in improved vascular mobility and tumor-homing potential of the cells. Therefore, here we tested the effects of MSCs in spheroids on growth and phenotype of various cancer cells. Within hanging drop co-cultures of MSCs and breast cancer cells (BCCs), the MSCs rapidly surrounded the BCCs and promoted formation of cancer spheroids then disappeared 24-48 hours later. Further experiments revealed that BCCs internalized and degraded MSCs in spheroids, a process resembling cell cannibalism/entosis. The resulting BCCs showed markedly delayed tumorigenicity after injection into mice and displayed features of cellular dormancy. Moreover, sphere-derived MSCs (SDMs) delivered intravenously effectively reduced growth of breast cancer metastasis in lungs of mice. Importantly high cell viability, small cell size, and elevated expression of tumor-suppressive factors were not diminished with cryopreservation of SDMs suggesting that cell banks can be prepared for ‘off-the-shelf’ patient therapies. The results here provide new insight into the interactions between MSCs and cancer cells and indicate that MSCs prepared as spheroids have enhanced tumor-suppressive properties. Collectively, 3-D cultures of MSCs and cancer cells are useful to model the tumor niche in further research and to effectively precondition MSCs for cancer therapies.

Biography:

Jan Habdas received his PhD (1978) from the University of Silesia, Department of Chemistry, Katowice, POLAND. He was a post-doctoral fellow and a research associate at Texas Tech University, Kansas State University and University of Idaho. Since 1990 his main scietific interest has been the synthesis of porphyrins in the aspects of their applications in cancer therapy. He synthesied a new group of porphyrin derivatives: phosphono- aminopeptidyl porphyrins.He published 62 papers in major peer reviewed reputable chemical, biochemical and medical journals. Among them 40 on synthesis, photochemical and medical properties of porphyrins. He is now retired.

Abstract:

Since 1903, when a Danish physician Niels Finsen was awarded the Nobel Prize in Phisiology-Medicine for his investigation on applaying light as a cure of skin cancer, and particularly since 1931, when a German chemist Hans Fischer was awarded the Nobel Prize for his work on haemin synthesis, the interest in synthesis of porphyrins with desired properties and their application in medicine has grown significantly. Addtionally, in the second half of the XXth century, photosensitizing properties of porphyrins have been found which combined with the use of laser light and its distribution by fabric optics gave the input for new methods of diagnosis and therapy of cancer. These methods include: Photodynamic Therapy (PDT), Photochemical Antimicrobial Chemotherapy, (PACT) and Photodynamic Distroying of Viruses (PDV). Our investigation of using amide, carboxy and phosphono derivatives of meso-tolyl and meso-piridylporphyrins showed them to be effective photosensitizers in the in vitro tests on MEL 45 and SKMEl 188 (human melanoma) causing a decrease in the number of cancer cells up to threefold. Phosphono derivatives of meso-piridylporphyrins showed a moderate inhibitory activity towards aminopeptidase N, which is responsible for tumor cells growth. The in vivo tests on mice manifested some toxic effects which are possible unwanted side effects.A known side effect during human therapy is photosensitivity of patients which lasts from two up to four weeks, during which time the patients need to be kept in dark rooms.

Biography:

Humayoon S. Satti is a PhD student at Quaid-i-Azam University, Islamabad, Pakistan. He is also working as a Scientific Officer at Armed Forces Bone Marrow Transplant Centre, Pakistan. He is a recipient of ASH visitor Training program 2011 and HEC indigenous Scholarship award (2009-14). He has published 9 papers in national and international journals and currently working as co-investigator in two phase-I/II human clinical trials exploring therapeutic potential of human mesenchymal stem cells in diseases like GVHD and spinal cord injury.

Abstract:

Introduction: Mesenchymal stem cells (MSC) transplantation has recently immerged as promising therapeutic approach to treat spinal cord injury. We report safety and preliminary findings on efficacy of intrathecal injection of cultured autologous bone marrow derived MSCs (BM-MSCs) in 10 patients suffering from spinal cord injury. All patients had traumatic spinal injury at thoracic level resulting in complete paraplegia. Patients received 3 doses of autologous BM-MSCs via intrathecal injection. Primary endpoint was safety which was documented by two independent neurologists four weeks after receiving last injection. ASIA scoring, MRI and neurophysiological tests were carried out before treatment and 12 months after receiving treatment. Results: The patients received at median 3 doses of 1.2 x106 MSCs/Kg body weight. The procedure was well tolerated in all subjects with no adverse event or serious complication observed during median follow up of 263 days (range: 100-602 days). Six patients suffered from chronic injury, with median duration of 33 months since time of injury (range: 10 to 55 months). Four of them have completed one year of follow up and two have displayed benefits in neurogenic bowel and bladder incontinence, besides limited improvement in hip flexor muscle power. However none has yet shown improvement in ASIA scale. Interestingly, all four patients with sub-acute injury showed some degree of improvement in sensory and motor functions in preliminary reports. These patients also exhibited improved bowel and/ or bladder control. Detailed report on efficacy will follow on completion of one year follow up of the remainder patients. Conclusion: This pilot study demonstrated that intrathecal administration of cultured autologous BM-MSCs is safe and feasible for treatment of spinal cord injury.

Biography:

Reham A Afify completed her PhD at the age of 24 years and postdoctoral studies from Cairo University School of Medicine. She is a assistant professor of clinical Pathology in Cairo university school of medicine and one of members of research workers in the bone marrow and stem cell transplantation unites in Alkaser Alaini university Hospital. She has published many issues in the field of bone marrow and stem cells transplantation and differentiation and also published more than 20 papers in reputed journals and has been serving as reviewers of some of them.

Abstract:

Biography:

Gallicchio earned his Ph.D. in Experimental Hematology at New York University Medical Center. He completed a fellowship in hematology at Memorial Sloan Kettering and Did post--‐graduate training at the University Of Connecticut Health Center. He received his Diploma in internal medicine from the “Vasile Goldis” University of Arad (Romania). He has published more than 160 scientific articles and book chapters and has received ten U.S. patents for discoveries focused on drug development for AIDS and cancer. He has served on the faculty of several American and international universities in Addition to serving as President of Alpha Eta Honor Society, the International Society For Lithium Research, and the International Federation of Biomedical Laboratory Science. He currently serves as Vice President, Educational and Research Centers in Trace Elements operated under UNESCO. He is a Fellow of the Association of Clinical Scientists, the Association of Schools of Allied Health Professions, and the Royal Society Of the Arts. In 2003, at the 200th anniversary of RSA, because of his long--‐standing effort To educate and train biomedical laboratory scientists from England, Dr. Gallicchio was recognized for his efforts by being presented to Her Majesty, Queen Elizabeth II.

Abstract:

Lithium (Li) salts have been widely used in psychiatry as mood stabilizing agents for 60 years. Li found in variable amounts in foods, especially grains, vegetables, and in some areas, the drinking water provides a significant source of the element. Therefore, dietary intake in humans depends on location, type of foods consumed, and fluid intake. Traces of Li have been detected in human organs and tissues, leading speculation that the element was responsible for specific functions in the human body. It was not until the 20th century that studies performed in the1970’s and 1990’s, primarily in rats and goats, maintained on Li-deficient diets demonstrated higher mortality, altered reproductive and behavioral abnormalities. Such deficiencies have not been detected in humans; however, studies performed on populations living in areas with low Li levels in water sup- plies have been associated with higher rates of suicides, homicides, and the arrests rate for drug abuse and other crimes. Li appears to play a significant role in early fetal development as evidenced by high Li levels during the early gestational period. Biochemically, the mechanism of Li action involves multi- factor and interconnected pathways with enzymes, hormones, vitamins, and growth and transforming factors. This body of evidence now appears sufficient to label Li as an essential element with the recommended RDA for a 70 kg adult of 1000 mg/day. Of extreme importance for the future is the growing body of evidence indicating Li can be used effectively for the treatment of acute brain injuries, e.g., ischemia and chronic neurodegenerative dis- eases such as Alzheimer’s disease, Parkinson’s disease, Tauopathies, and Huntington’s disease. This conclusion is based upon evidence showing Li as important in neurogenesis as well as protecting neurons from neurotoxicity. Li influences stem cells, both neuronal and marrow derived, thus additional therapeutic implications for this element in clinical medicine to treat disorders associated with the faulty production of blood and nerve cells or as a tool to enhance blood stem cell mobilization for transplantation.

Biography:

Xiao received a Doctor of Natural Science Degree from Swiss Federal Institute of Technology, Zurich. He is current Professor in Monash University. He is the CEO & CFO of iNovaFarm, a premier Bio-Tech company. He has published more than 100 papers in reputed journals and serving as editorial board members of more than 10 journals.

Abstract:

Appropriate connections or interactions among different neural cell types are essential for the correct and efficient functioning of the nervous system during development and regeneration after trauma or degeneration. The aim of my research is to understand the molecular events that mediate communication among neural cells in the nervous system during development, myelination, learning and memory, degeneration, and regeneration. These studies have yielded insights into the therapeutic potential of cell signalling molecules to ameliorate or even ablate the detrimental consequences of nervous system injury and neurodegenerative diseases, including stroke, traumatic brain injury, spinal cord injury, Alzheimer Disease (AD), and Multiple Sclerosis (MS). Using genome-wide chromatin immunoprecipitation approaches, we found that AICD is specifically recruited to the regulatory regions of several microRNA genes, and acts as a transcriptional regulator for miR-663, by which suppresses neuronal differentiation in human neural stem cells. We have generated transgenic pigs expressing mutant G93A hSOD1 and showing hind limb motor defects, which are germline transmissible, and motor neuron degeneration in dose- and age-dependent manners. Furthermore, in a case report we present the treatment of aggressive MS patient with multiple allogenic human umbilical cord-derived mesenchymal stem cell and autologous bone marrow-derived mesenchymal stem cells over a 4 y period. The treatments were tolerated well with no significant adverse events. Clinical and radiological disease appeared to be suppressed following the treatments and support the expansion of mesenchymal stem cell transplantation into clinical trials as a potential novel therapy for patients with aggressive MS.

Biography:

Dinulescu is an Assistant Professor at Harvard Medical School. She received her Ph.D. from Oregon Health and Science University and completed her postdoctoral studies in the field of Cancer Genetics at MIT. Dr. Dinulescu’s research interests focus on cancer biology, malignancies of the gonads and reproductive tract, with a special emphasis on ovarian cancer research and endometriosis. Our laboratory is actively investigating the key contribution of cancer stem cells (CSCs) to tumor chemoresistance. Our current studies focus on better understanding the mechanism of stem cell signaling in the maintenance of the CSC niche and ovarian tumorigenesis. The aim is to harness the power of nanotechnology to develop improved “homing” technologies for the delivery of therapeutic agents specifically targeting and sensitizing ovarian cancer cells, including CSCs, in a spatio-temporal fashion.

Abstract:

Cancer stem cells (CSCs) are considered to be important for tumor development, metastasis, and chemoresistance based on their key ability to survive standard cancer chemotherapies. Multiple studies have now defined CSCs as having an increased tumorigenic ability in serial transplantation experiments conducted in tumor xenografts. This assay, however, may not be entirely accurate in clearly identifying CSCs. Nevertheless, there is enough evidence to support the idea that CSCs are necessary to initiate and propagate tumor diversity. In addition, CSCs are studied in multiple solid tumors, including ovarian cancer, due to their intrinsic chemoresistance properties. Thus, while non-CSCs have been shown to be sensitive to available therapies, CSCs are enriched in response to treatment and regenerate an increasingly platinum resistant tumor. Furthermore, similar to normal stem cells, CSCs are likely shielded from damage and injury by the tumor niche microenvironment, which makes it difficult to target them therapeutically. The cellular origin of ovarian cancer stem cells has been difficult to identify. Multiple stem cell models have been proposed. One model proposes that CSCs can originate either from somatic adult stem cells or from progenitor non-stem cells. The ovarian surface epithelium and distal fallopian tube, which are tumor initiation sites, consist of both adult stem cells and also progenitor cells that are relatively undifferentiated and capable of differentiating into distinct morphological subtypes. We have recently found that ovarian cancer and somatic stem cells share common molecular pathways and markers, which is consistent with the model that some cancer stem cells may either arise from adult stem cells or most likely evolve to mimic somatic stem cell properties.

Biography:

Alan Wells, M.D., D.M.Sc., is Executive Vice-Chair and Thomas J Gill III Professor of the Departments of Pathology and BioEngineering. Wells holds an A.B. in Biochemistry from Brown University (1979), a D.M.Sc. in Tumor Biology from the Karolinska Institute (1982), and an M.D. from Brown University (1988). Following his studies, Dr. Wells completed a postdoctoral Fellowship in Tumor Biology at the University of California in San Francisco, California, and a Residency in Laboratory Medicine at the University of California in San Diego, California. He has over 230 scholarly publications that have been cited over 15,000 times. These advances have been recognized by numerous grants, patents, and invited keynote talks and professorships, as well as election to the American Society for Clinical Investigation and the American Association of University Pathologists (Pluto Club). He has consulted extensively to industry and has cofounded two companies. None of this would have been possible without the input, aid, and assistance of some 20 graduate students (PhD and MD-PhD) and a similar number of post-doctoral fellows and a half dozen junior faculty colleagues.

Abstract:

Transplantation of stem cells to augment the intrinsic regenerative capacity is a potential therapy for non-healing wounds. However, such approaches have been less than successful, as the majority of introduced cells are lost within days due to cell death from the harsh wound environment that lacks nutrients and presents apoptosis-inducing cytokines. A cellular engineering approach to enhanced survival could overcome this obstacle. Activation of the EGF receptor at the cell surface, but not from internalized receptors in the endosomes, promotes cell survival in the face of cellular starvation, death cytokine signaling, and toxic agents. The signaling cascade involves tonic low-level activation of Erk MAPK and PI3K/Akt pathways. To achieve this mode of signaling the triggering ligand must be retained in or attached to the substratum or matrix. This can be accomplished by either tethering classical EGF receptor ligands to the substratum, or activating the EGF receptor with cryptic ultralow affinity matrikines present in tenascin-C and laminin V. We have creating matrices with (or without) tethered EGF or tenascin-C. These were introduced into acute full thickness wounds in mice, internal soft tissue in mice (subfascial), and critical cortical bone defects in dogs. In all three instances wound healing and vascularization was significantly increased in the presence of EGF receptor ligand. Xenotransplanted stem cells were retained up to one month in immunocompetent mice, compared to less than a week without the tEGF or tenascin-C. The presence of these cells with the tenascin-C limited scarring in a hypertrophic scar model, even 6 months after wounding, when all the transplanted stem cells have been rejected. The extended survival of these transplanted stem cells allows them to educate the local wound environment, and turn the healing towards regeneration and away from non-functional scarring or failure to heal. This represents a new approach to cellular support for dysrepair.

Biography:

Patricia Berg received her bachelor’s degree in mathematics from the University of Chicago, her Ph.D. in microbiology from the Illinois Institute of Technology, then pursued Post Doctoral studies at the University of Chicago. Research at the National Institutes of Health followed. Currently she is a Professor of Biochemistry and Molecular Medicine at George Washington University in Washington, DC, where she is director of a cancer research laboratory. Her work, which centers on BP1, has been published in major journals and has been featured on network television and in major media, including the New York Times and Washington Post.

Abstract:

BP1, a transcription factor (TF) we identified in cancer, is encoded by a homeobox gene. BP1 is overexpressed in breast cancer, prostate cancer, ovarian cancer, acute myeloid leukemia, non-small cell lung cancer, and possibly other malignancies as well. Important characteristics of BP1 in breast cancer, a focus in our laboratory, include findings that: (1) BP1 is expressed in 80% of invasive ductal breast tumors, including 89% of the tumors of African American women compared with 57% of the tumors of Caucasian women. (2) BP1 expression correlates with the progression of breast tumors, from 0% in normal breast tissue to 21% in hyperplasia and 46% in ductal carcinoma in situ. (3) Expression of BP1 is associated with larger tumor size in both women and mice. (4) BP1 appears to be associated with metastasis. Forty-six cases of inflammatory breast cancer were examined and all were positive for BP1 expression, as well as matched lymph nodes in the nine metastatic cases. (5) BP1 overexpression induces oncogene expression. BP1 activates the BCL-2 gene; high BCL-2 protein levels are associated with resistance to drug and radiation therapy. BP1 also activates VEGF and c-MYC, as well as other genes important in angiogenesis, invasion and metastasis. Interestingly, BP1 down-regulates BRCA1. (6) BP1 up-regulates ER alpha, inducing estrogen independence and tamoxifen resistance. In summary, BP1 appears to confer properties on breast cancer cells that lead to a more invasive and aggressive phenotype. Since the functions of homeotic TF are highly conserved, it is likely that BP1 regulates many of the same processes and genes in other malignancies in which it is active.

Biography:

Purwati Armand has finished in general practitioner from Airlangga University in 1997, has completed in internal med. Specialist in 2008 from Airlangga University also and taken Doctoral program in Airlangga University 2010-2012. Interest in stem cell field from 2008, be secretary of stem cell laboratory of Airlangga University and also secretary of Surabaya Regenerative Medicine Centre. Have almost 50 publication in journals, papers, and seminar.

Abstract:

Brain in control centre of the body, this organ has a wide range of responsibilities from coordinating our movement to manage our emotion, the brain does it all. For almost hundred years it has been a mantra of biology that brain cell do not regenerate so need to add new neuron when the brain injury but stem cell niche will induce endogenous stem cell in SVZ to regenerate it. Stem cell niche with content of GABA, FGFs, EGF, VEGF, PEDF. Parkinson’s involves the malfunction and death of vital nerve cells in the brain, called neurons. Parkinson's primarily affects neurons in an area of the brain called the substantia nigra. Some of these dying neurons produce dopamine, a chemical that sends messages to the part of the brain that controls movement and coordination. As PD progresses, the amount of dopamine produced in the brain decreases, leaving a person unable to control movement normally. Objective of this research to drive neuron progenitor stem cell from adipose to treat Parkinson. Adipose was isolation from patient and cultur become neuron progenitor stem cell, after second passage the neuron progenitor stem cell was harvesting . Neuron progenitor stem cell was characterized by Noch1 flowcitrometry and LDopa Icc. Neuron progenitor stem cell was produce dopamine ready implant for Parkinson patient by direct implantation. Result: Ten patients with Parkinson diseases with inclusion and exclusion criteria, received neuron progenitor cell implantation, 2 patients no significant improvement and 8 patients have significant improvement, outcome evaluating using mRS (Modified Ranking Scale) and BI (Barthel index ). Conclusion: Neuron progenitor stem cell has significant improvement for Parkinson diseases

Biography:

Mennat-allah Elmenyawi is a Assistant lecturer of medical physiology in faculty of medicine-Suez Canal University. She completed her Master degree in 2015, she also attended Workshops such as: bioinformatics and leadership and management in faculty of medicine-Suez Canal University, headache management workshop held in turkey in 2015 (African-turkish association of headache) and Conferences: fourth annual African association of physiology in 2012.

Abstract:

Introduction: Cell transplantation using The Bone Marrow Mesenchymal Stem Cells (BMSCs) and The Schwann Cells (SCs) to alleviate neurological deficits has become the focus of research in regenerative medicine. In attempt to identify the possible mechanisms underlying the regenerative potential of cell transplantation (BMSCs and SCs), this study investigate the most effective therapy of the sole cell transplantation (BMSCs and SCs) by induction of injury in rat’s sciatic nerve, when compared to their co-transplantation. Materials and methods: In this comparative experimental study, adult male albino rats (n=60, 250-300gm) divided into 5 groups: group (I): the control intact sciatic nerve, group (II): the left injured sciatic nerve injected intralesionally with physiological saline, group (III): the left sciatic nerve injected intralesionally with BMSCs, group(IV): the left sciatic nerve injected intralesionally with SCs, group(V): the left sciatic nerve injected intralesionally with BMSCs and SCs. BMSCs and SCs were labeled with Bromodeoxyuridine (Brdu). After 12 weeks, nerve conduction velocity, electromyographic, functional assessments, oxidative and antioxidative effects of cell tranplantation and measurement of BDNF were performed and analyzed by one-way analysis of variance (ANOVA). Results: This treatment led to: (i) improved walking tract as measured by sciatic nerve index in all the treated groups, (ii) increase in nerve conduction velocity and EMG magnitude by using biopack MP150 signifcantly (p<0.01) in SCs and Co-treated groups, (iii) increase in the antioxidant effect and reduction in the oxidative effect of cell transplantation in nerve tissue significantly (p<0.01) in BMSCs and Co-treated groups, (iiii) increase expression of brain derived neurotrophic factor (BDNF) in nerve tissue using real time PCR significantly (p<0.01) in SCs and Co-treated groups. Discussion: The results showed the superiority of the co-transplantation group followed by SCs group in the most of the assessments to BMSCs group which exceptionally succeeded in the increase of the antioxidant and the decrease in the oxidant levels.

Biography:

Zahara Mansoor has completed her masters in Regenerative Medcine at the Faculty of Medicine, University of Colombo who is currently drafting her thesis and will be graduating next year in 2016.She is one of the pioneering Stem Cell Scientist in Sri Lanka where stem cell is still at its infancy stage.Prior to this, I have successfully completed a Bachelor of Science, in Biotechnology at University of Bangalore. She also won the 2nd place for the Best Poster Presentation at The Annual Research Symposium, University of Colombo, 2015.Her interest motivated to explore research opportunities in the field of Regenerative Medicine.

Abstract:

Mesenchymal Stem cells (MSCs) are plastic-adherent, fibroblast – like cells with specific surface phenotype, having ability to differentiate into osteoblasts, chondroblasts and adipocytes in-vitro. Umbilical cord (UC) is a readily available without ethical constraints, showing high proliferation rate and osteogenic potential. To derive MSCs from the human UC Wharton’s Jelly (WJ) and osteogenic differentiation was my main objective.Following obtaining ethical approval, five UCs from healthy mothers undergoing elective Caesarian sections were collected, cleaned with phosphate buffered saline, removed blood vessels,digested WJ in 0.5% collagenase 2-3 hours / 0.2% collagenase overnight and cultured in DMEM supplemented with 10% FBS, 1% L-glutamine and 1% penstrep at 37Ëš C in 5% CO2. Cells are passaged at 70%confluency. At fourth passage (P4), osteogenic differentiation medium was added following incubation .Culture maintained for 21 days and cells were stained with 2% Alizarin red and von kossastains.MSCs were determined and characterized using Trypan blue test, Flow cytometry, RT-PCR and karyotypic analysis.Cells were were positive for CD90, CD73 and CD105 and negative for CD34 and CD45 markers expressing Oct-4 and G6PD genes. Karyotypes depicted were normal. Alizarin red stain gave bright orange red and von kossa stain gave black-brown deposits demonstrating the presence of extracellular calcium deposits.UC-MSCS serves as a suitable source for osteogenic regeneration Gene expression demonstrated the embryonic origin of the MSCs which maintained genomic stability upto P4 stage.So my initatiative stem cell research in Sri Lanka improves the therapeutic potential in bone defects and opens up new perspectives for bone tissue engineering.

Biography:

Zhiheng Xu was awarded an MD in 1989 from the Second Military Medical University, Shanghai, and a PhD in 1999 from Rutgers University, New Jersey.In 1999 he was a postdoctoral and research associate at Columbia University, New York.He received the Ruth L Kirschstein National Research Service Award in 2003 and the Distinguished Young Investigator Award, National Science Foundation (China), in 2007.

Abstract:

Human autosomal recessive primary microcephaly (MCPH) is a neural developmental disorder hallmarked by significantly reduced brain size and variable intellectual disability. Mutation of WD40-repeat protein 62 (WDR62) is the second major cause of MCPH. We have reported recently that WDR62 regulates the maintenance of neural progenitor cells (NPCs) during cortical development through JNK1 (Xu et al., Cell Reports 2014). However, the detailed biological function of WDR62 and the underlying mechanism by which WDR62 regulates JNK signaling are still not very clear. Here, we demonstrate that MEKK3 forms a complex with WDR62 to promote JNK signaling synergistically and regulate neurogenesis as well as brain size. MEKK3, WDR62 and JNK1 depletion or knockout phenocopy each other in defects including premature NPC differentiation and reduced brain size. These defects can be rescued by the expression of transgenic JNK1, indicating that the complex controls neurogenesis through JNK signaling. We show further that WDR62 protein level is positively regulated by MEKK3 through JNK1-induced WDR62 phosphorylation. Meanwhile, WDR62 is also negatively regulated by specific phosphorylation of WDR62 at T1053, leading to the recruitment of the E3 ligase FBW7 and proteasomal degradation of WDR62. Our findings demonstrate that WDR62 controls the maintenance of NPCs via MEKK3 and JNK1 during cortical development and reveal the molecular mechanisms underlying MCPH pathogenesis.

Biography:

Professor Simon Berkovich received MS in Applied Physics from Moscow Physical-Technical Institute (1960) and PhD in Computer Science from the Institute of Precision Mechanics and Computer Technology of the USSR Academy of Sciences (1964). He has several hundred publications in various areas of physics, electronics, computer science, and biology. In 2002, Professor Simon Berkovich was elected a member of the European Academy of Sciences "for an outstanding contribution to computer science and the development of fundamental computational algorithms". In 2014, he won the GWU Technology Transfer Innovation Competition. In 2015, he was awarded a status of Emeritus Professor

Abstract:

Modern science resolutely rejects the longstanding belief that understanding of Life needs some ‘vital’ force besides fundamental physics concepts. However, an essential part of biological processes still cannot find a concrete physical explanation. So, physics that does not provide an explanation for biology is not just incomplete, it merely employs an incorrect paradigm. Therefore, right understanding of biology may help to straighten physics, rather than vice versa. The essence of biology lies in information processing. Likewise, it is also supposed “The physical world is made of information with energy and matter as incidentals” (John A. Wheeler). Scientific views often go in parallel with contemporary technologies; correspondingly, at different times living organisms were compared to mechanical apparatuses, hydraulic systems, clock devices, chemical factories, electrical machines, computers etc. Nowadays, the Information Revolution fosters Cloud Computing. This inspires to consider the Universe as an Internet of Things. Such kind of an arrangement is realized in the construction of Holographic Universe arising from our Cellular Automaton model of physics. Workings of interactive holography attain a clear explanation for the strangeness of quantum mechanics, particularly, for the most inconceivable property of nonlocality. Further, in contrast to quantum particles, macromolecules can acquire a content-addressable access to holographic memory, leading to the capabilities of sophisticated behavior. Thus, the Holographic Universe presents an operational framework for biological processes. Instruction sequences for biological objects include signals for information control and impacts for material actuations. Revealing a physical facility that could intervene in this process may provide a new approach to medical treatment.

Biography:

Carol M. Jim is currently a Ph.D. candidate working on her dissertation at The George Washington University in the School of Engineering and Applied Science. She is also an adjunct professor of computer science and information technology at Hood College where she received her M.S. in computer science and B.A. in mathematics. She has published in peer-reviewed international conference proceedings and journals on topics including network forensics, data mining and machine learning, game theory, and computational biology.

Abstract:

Although extensively studied, little is still known about the origins of pairs of monozygotic twins and higher order multiples such as triplets and quadruplets. By understanding the mechanism behind the twinning process, further developments in developmental biology can be achieved as well as insights into disease mechanisms and the human aging process. We consider and analyze certain possible cell labeling schemes that model an organism’s development and expose the phenomenon of quadruplet twins during the process. We predict that monozygotic quadruplets are not quadruplets in the traditional sense but rather, are two pairs of monozygotic twins where the pairs slightly differ. The probability of monozygotic twins is discovered to be (1/2)K, and the probability of monozygotic quadruplets, or triplets in the case of the death of an embryo, is found to be (1/8)K, where K is a species-specific integer representing the number of pairs of homologous chromosomes. This investigation into twinning establishes the cell development mechanism. The failure of the internal cellular clock from this mechanism may play an important role in cancerogenesis. The parameter K may determine cancerization with a probability threshold that is approximately inversely proportional to the Hayflick limit, so exposure to small levels of ionizing radiation and chemical pollution may not produce cancer. From the considered model, the mechanism involved in the two opposite circumstances of twinning and cancerogenesis provides a foundation for the understanding of the origins of these two disparate processes.

Biography:

Miguel Garber has over 30 years experience in Internal medicine and cardiology, with expertise in regenerative medicine and research. He has more than 10 years experience working with stem cells, including exploring and developing stem cell therapies for cardiomyopathies, osteoarthritis and regenerative medicine at Stem Cell Therapeutics Department of American Medical Information Group and Clinica Quirurgica Quantum. He is currently serving as Medical Director of Revitacell and Clinical Director of Regenerative Medicine department at Humanus. Dr. Garber has made a significant contribution to Stem cell Research and is actually he is involved in Adipose Stem Cell application.

Abstract:

A comprehensive review of the stem cell research literature indicates that bone marrow stem cells (BMSC) constitute the natural repair system of the body and that the number of circulating stem cells appears to be a critical parameter in the effectiveness of stem cell-based tissue repair. On this basis, Endogenous Stem Cell Mobilization (ESCM) emerges as a possible approach to the treatment of a variety of degenerative conditions, including diabetes. BMSC have been shown to have the ability to migrate on their own into the pancreas and to differentiate into functional insulin-producing cells, and mobilization of BMSC has been shown to rescue streptozotocin-induced diabetes in mice. The stem cell mobilizer StemEnhanceTM increased the number of circulating stem cells as well as the number of stem cells that migrated in the pancreas of streptozotocin-treated mice, which significantly increased insulin production and reduced fasting blood glucose. This was confirmed in humans where StemEnhanceTM supplementation for 12 weeks decreased fasting blood glucose and HbA1c levels in type II diabetes patients. A multi-center study is underway to document the effect of plant-based stem cell mobilizers on pre-diabetes. Current evidence suggests that ESCM could be an effective approach to prevent or slow down the development of diabetes, or in certain cases even reverse diabetes.

Biography:

I am practicing as an assistant professor in Oral & Maxillofacial surgery department of Isfahan university of medical sciences since 2010 while seeking further training and experience in Craniofacial cleft surgery.My project for getting oral and maxillofacial specialist degree entitled “ A comparison of tissue-engineered bone from adipose-derived stem cell with autogenous bone graft…” has been done in May 2010. This topic with its special harvest of stem cell from adipose tissue for maxillofacial reconstruction has been done for the first time in Iran and the world .It has been published in International journal of oral and maxillofacial surgery 2012.

Abstract:

This study was designed to compare bone regeneration of tissue-engineered bone from adipose-derived stem cell and autogenous bone graft in a canine maxillary alveolar cleft model. In this prospective clinical trial, mesenchymal stem cells (MSCs) were isolated from subcutaneous canine adipose tissue. Undifferentiated cells were incubated with a 3 mm × 3 mm × 3 mm hydroxyapatite/beta-tricalcium phosphate scaffold, in specific osteogenic medium for 21 days. Four mongrel dogs were prepared by removal of two of the three incisors bilaterally and a 15 mm defect in bone was created from crest to nasal floor. After healing, repair was followed by a tissue engineered bone graft from adipose-derived stem cells on one side and corticocancellous tibial auto graft on the other side. Bone regeneration was evaluated by histomorphometry on days 15 and 60 after implantation. The data were analysed with descriptive and t test methods (α = 0.05). Bone formation on the autograft sides was higher than on the stem cell sides at 15 and 60 days, 45% and 96% versus 5% and 70%, respectively. Differences between the two groups at 15 and 60 days were significant (p = 0.004 and 0.001, respectively). Although autograft is still the gold standard for bone regeneration, tissue engineered bone may provide an acceptable alternative.

Biography:

Atefeh Roein Tan has completed her Master in Biotechnology at the age of 29 years from Payame Noor University of Tehran. She work as a researcher and lab technician for more than four years in Shefa Neuroscience Research Center in Tehran, Iran. She worked on the project of creating and purifying neural cells and using in the treatment of Amyotrophic lateral Sclerosis as a technician and this project has been patented in September of 2014.

Abstract:

Cell therapy is one of the approaches for the treatment of locomotive deficits in spinal cord injuries and neurodegenerative disorders. Neural stem cells derived from bone marrow stromal cell are considered as a feasible option for cell therapy. Epigenetic experts have reported that cell differentiation during the development process of BMSCs to NSCs is controlled by several factors including growth and environmental factors as well as regulation and induced effects. Several protocols are using different chemicals for inducing neuronal differentiation of BMSCs. In this study, we investigated the feasibility of using of Selegiline as an efficient inducer for neuronal differentiation of rat BMSCs and its effect on gene expression of neurotrophins and their receptors. Based on our results, Selegiline has multiple effects which makes it a good candidate for inducing neuronal phenotype into BMSCs. Also it has ability to induce the expression of some genes like neurotrophic factors. Therefore, it can be considered as an alternative neuroprotective inducer for BMSCs where the induced cell can still be used for cell therapy. Moreover, the local expression of neurotrophin genes suggests a wide range of paracrine and/or autocrine mode of action through their corresponding receptors within the bone marrow. For our experiments, after achieving the optimal concentration of Selegiline the expression of antibodies Nestin , Neurofilament 68,Neurofilament 200, TH, Neu-N and GFAP was evaluated using immunocytochemistry. Furthermore, the expression profile of neurotrophins NGF, BDNF and NT-3 and their receptors (TrkA/B/C, p75NTR) was examined during neural differentiation by RT-PCR.

Biography:

Kevin Murray, Sales Manager for BioSpherix, Ltd. BS BioChemistry, MBA Finance & Marketing, 20+ Years experience in the Pharmaceutical/Biotech/Medical Research Industry.

Abstract:

Total quality recognizes that for best cell potency, cells need full-time optimization of all critical cell process parameters (O2, CO2, RH, T). Total quality recognizes that all typical negative side effects of machines on cells (particles, heat, vibration, etc.) must be neutralized to make automation compatible with a cell optimized ecosystem, and those machines must be protected from dust, aerosols, and corrosion. Total quality recognizes that each entire cell production line (all manual and automated steps) must be protected from microbial contamination by full-time, absolutely aseptic conditions. Total quality recognizes that all personnel must be fully protected from cells harboring virus, vectors, prion, and other pathogens. Total quality recognizes that scaling up and out must be efficient. Total quality recognizes that cost efficiency is a fundamental quality attribute, critical for commercial. The Xvivo System is a comprehensive, modular, total quality "platform" for cells.

Biography:

Mahsa Khayat-Khoei has completed her medical education and received her MD degree from Shahid Beheshti University of Medical Sciences in 2012. She will soon receive her MBA degree, and is a research assistant at University of Texas Health Science Center. She has worked as a researcher and clinical trainee at Baylor Saint Luke's Medical Center, as well as a research trainee at MD Anderson Cancer Center in Houston, Texas. She has a patent, several publications in reputed journals and has presented her research in respectable national and international meetings. She has been serving as an editorial board member of several medical journals. Her main research interest is on Amniotic Membrane derived Stem Cells and their different properties.

Abstract:

Human placenta supports the growing fetus and consists of several layers the inner most of them is a membrane with unique capacities. This layer which is called the Amniotic membrane (AM) develops two different types of pluripotent stem cells which have previously shown to express angiogenesis regulatory properties that make them great candidates for cancer and cardiac researches. In order to store and transfer these cells for experimental and possible clinical purposes, cryopreservation is a necessary procedure. However it is debatable whether the cryopreservation negatively influences the Amniotic membrane Stem Cells (AMSCs) characteristics or not. In this study AMSCs were cryopreserved and stored for 6 months at -80 °C. The effect of cryopreservation on these stem cells’ properties was evaluated by comparing the angiogenesis activity of the thawed AMSCs and fresh AMSCs in an animal model. The length and number of branches of formed capillaries were measured via intra-vital microscopy after 5 and 15 days. The amount of angiogenesis promoting factors IL-8 (interleukin-8) and TIMP-2 (Tissue Inhibitor of Matrix Metalloproteinase-2) that are believed to be produced mainly by AMSCs were evaluated using ELISA assay. The effect of cryopreserved AMSCs on angiogenesis was reported to be of similar power to that of fresh cells. These promising results can act as a basis to confirm cryopreservation as a proper and reliable method of storing AMSCs in different clinical and research settings.

Biography:

Khalid Shah heads the Molecular Neurotherapy and Imaging Laboratory in the departments of Radiology and Neurology at Massachusetts General Hospital. Dr. Shah is also the Director of the Stem Cell Therapeutics and Imaging program in the Center for Translational Research at MGH and also a Principal Faculty at Harvard Stem Cell Institute in Boston. His laboratory focuses on developing therapeutic stem cells for receptor targeted therapies for cancer and testing their efficacy in clinically relevant mouse tumor models. Dr. Shah’s research also explores the development of novel in vivo imaging markers and their potential use in assessing fate of stem cells and their therapeutic efficacy. In recent years, Dr. Shah and his team have pioneered major developments in the stem cell therapy field, successfully developing experimental models to understand basic cancer biology and therapeutic stem cells for cancer, particularly brain tumors. These studies have been published in a number of very high impact journals like Nature Neuroscience, PNAS, Nature Reviews Cancer, JNCI, Stem Cells and Lancet Oncology, validating the use of therapeutic stem cells alone and in combination with clinically approved drugs for cancer therapy. Dr. Shah holds current positions on numerous councils, advisory and editorial boards in the fields of stem cell therapy and oncology. In an effort of to translate the exciting therapies develped in his laboratory into clinics, he has recently founded biotech company, AMASA Technologies Inc. whose main objective is the clinical translation of therapeutic stem cells in cancer patients.

Abstract:

Stem cell-based therapies are emerging as a promising strategy to tackle cancer. Multiple stem cell types have been shown to exhibit inherent tropism towards tumors. Moreover, when engineered to express therapeutic agents, these pathotropic delivery vehicles can effectively target sites of malignancy. Using our recently established invasive, recurrent and resection models of primary brain tumors (GBM) and breast and melanoma metastatic tumors in the brain that mimic clinical settings, we show that that engineered human mesenchymal stem cells and neural stem cells expressing novel bi-functional proteins or loaded with oncolytic viruses target both the primary and the invasive tumor deposits and have profound anti-tumor effects. These studies demonstrate the strength of employing engineered stem cells and real time imaging of multiple events in preclinical-therapeutic tumor models and form the basis for developing novel cell based therapies for cancer. This presentation considers the current status of stem cell-based treatments for tumors in the brain and provides a rationale for translating the most promising preclinical studies into the clinic.

Biography:

Jaroslaw Blaszczyk has completed his PhD at the age of 30 years from Technical University of Lodz and postdoctoral studies from NIH, National Cancer Institute at Frederick. He became a research assistant professor at Michigan State University. After that he served as the PDB annotator at Rutgers University of New Jersey. Currently he is an assistant professor at the Centre of Molecular and Macromolecular Studies of the Polish Academy of Sciences. He has published more than 67 papers in reputed journals and has been serving at several grant review panels at NCN, the Polish National Science Center.

Abstract:

We discovered the new, hexagonal crystal form of lipase B from Candida antarctica (CAL-B). The NAG (N-acetyl-D-glucosamine) molecules, which were closing the glycosylation site in the orthorhombic form, in our hexagonal structure, unexpectedly, adopt an open conformation. We do not know whether the opening and closing of the glycosylation site by the ‘lid’ NAG moiety, could be related to the opening and closing of the active center of the enzyme upon substrate binding and product release. The packing of molecules in the hexagonal crystal makes the active center of the enzyme very well accessible for the ligand, which, in our opinion, may help in the enzyme-ligand complex formation. Financial support by the Polish National Science Center, grant No. DEC-2012/05/B/ST4/00075, is gratefully acknowledged. The structure is available at the PDB, entry 4ZV7.

Biography:

For 20 years, he has been developing gene and cell therapy to protect against the side effects of radiation. He collaborates with clinicians to develop new strategies for treatment of patients after radiotherapy overexposures. He has participated in the first establishment of proof of concept of the therapeutic efficacy of Mesenchymal stem cells (MSCs). Currently his work focuses on the development of radio-induced bone marrow aplasia using human hematopoietic stem cells derived from human IPS. He is a member of various learned national and international societies and associate editor of international journals. Hirsch Index 22.

Abstract:

Institute of Radioprotection and Nuclear Safety Radiotherapy may induce irreversible damage on healthy tissues surrounding the tumour. It has been reported that the majority of patients receiving pelvic radiation therapy shows early or late tissue reactions of graded severity as radiotherapy affects not only the targeted tumor cells but also the surrounding healthy tissues. The late adverse effects of pelvic radiotherapy concern 5 to 10% of them, which could be life threatening. However, a clear medical consensus concerning the clinical management of such healthy tissue sequelae does not exist. Although no pharmacologic interventions have yet been proven to efficiently mitigate radiotherapy severe side effects, few preclinical researches show the potential of combined and sequential pharmacological treatments to prevent the onset of tissue damage. Our group has demonstrated in preclinical animal models that systemic MSC injection is a promise approach for the medical management of gastrointestinal disorder after irradiation. We have shown that MSC migrate to damaged tissues and restore gut functions after irradiation. We carefully studies side effects of stem cell injection for further application in patients. The clinical status of four first patients suffering from severe pelvic side effects resulting from an over-dosage was improved following MSC injection in a compassional situation. Bone marrow-derived MSC from the patients´ children were injected to four patients. A quantity of 2 millions to 6 millions of MSC /kg were infused intravenously to the patients. Pain, hemorrhage, frequency of diarrheas and fistulisation as well as the lymphocyte subsets in peripheral blood were evaluated before MSC therapy and during the follow-up. Two patients revealed a substantiated clinical response for pain and hemorrhage after MSC therapy. In one patient pain reappeared after 6 months and again substantially responded on a second MSC infusion. A beginning fistulisation process could be stopped in one patient resulting in a stable remission for more than 3 years of follow-up. The frequency of painful diarrhea diminished from an average of 6/d to 3/d after the first and 2/d after the 2nd MSC injection in one patient. A decline of CD4+ and CD8+ T lymphocytes and an increase of potentially regulatory CD25+ T cells accompanied the clinical response in this patient after the MSC injections. In all patients, prostate cancer remained in stable complete remission. A modulation of the lymphocyte subsets towards a regulatory pattern and diminution of activated T cells accompanies the clinical response in refractory irradiation-induced colitis. No toxicity occurred. MSC therapy was safe and effective on pain, diarrhea, haemorrhage, inflammation, fibrosis and limited fistulisation. For patients with refractory chronic inflammatory and fistulising bowel diseases, systemic MSC injections represent a safe option for salvage therapy. A clinical phase II trial will start in 2016.

Biography:

Mohammadhadi fartookzade has Msc degree in MBA and B.s. degree in Micribiologgy. He is the technician in Electron microscope unit. He is working in Iran university of Medical Sciences.

Abstract:

Neural stem cells (NSCs) find in the sub-ventricular zone (SVZ) and the hippocampus of the adult brain. NSCs can give rise to neurons, astrocytes and oligodendrocytes. Locus Ceoruleus (LC) plays an important role in the sleep-wake cycle. The aim of this investigation was study of effect of Neural Stem Cells (NSCs) transplantation on the sleep-wake cycle after bilateral lesion of the locus coeruleus. Fourty-two adult male Wistar rats, were categorized in seven groups [Control, Sham (cannula implantation), lesion, experimental 1 (intravenous transplantation of NSCs), experimental 2 (intravenous transplantation of noradrenergic-like cells (NACs)), experimental 3 (intraventricular transplantation of NSCs), experimental 4 (intraventricular transplantation of NACs)]. Neural stem cells were harvested from SVZ of newborn rat brains. NSCs were differentiated in neurobasal medium, B-27 supplemented with BDNF and GDNF for 5 days. The animals received bilateral 6_hydroxydopamine (6_OHDA) lesion of the LC. For sleep-wake recording 3 EEG and 2 EMG electrodes were implanted. In this study Nestin and Sox2 were expressed in NSCs. NSCs were differentiated into NACs and Tyrosine hydroxylase was detected in these cells. A significant decrease was seen in NREM (Non Rapid Eye Movement) and PS (Paradoxical Sleep) stages and a significant increase was seen in wake and PS-A (Paradoxical Sleep without Atonia) in lesion group in comparison with control and sham groups (P≤0.05). NSCs transplantation in experimental groups prevented of decrease in PS and increase in PS-A (P≤0.05). The results of this study demonstrate NSCs have ablility to differentiate into noradrenergic cells and NSCs transplantation improved disruption of the sleep-wake cycle after bilateral lesion of LC.

Biography:

Purita is director of Institute of Regenerative and Molecular Orthopedics. The Institute specializes in the use of Stem Cells and Platelet Rich Plasma injections. Dr. Purita is a pioneer in the use of Stem Cells and Platelet Rich Plasma. He received a B.S. and MD degree from Georgetown Univ. Dr. Purita is board certified in Orthopedics by ABOS. He has fellowships in the American College of Surgeons, American Academy Orthopedic Surgeons, and American Academy of Pain Management. He has lectured and taught extensively throughout the world on the use of Stem Cells and Platelet Rich Plasma as a visiting professor. He has been instrumental in helping other countries in the world establish guidelines for the use of Stem Cells in their countries.

Abstract:

The presentation concerns cutting edge aspects of PRP and Stem Cell (both bone marrow and adipose) injections for musculoskeletal conditions in an office setting. Indications are given as to which type of cell and technique to use to accomplish repair. Stem cells, both bone marrow derived (BMAC) and adipose, are used for the more difficult problems. PRP injections are utilized for the less severe problems. Indications are given when to use Stem Cells verses PRP and when to use both. The newest concepts in stem cell science are presented. These concepts include the clinical use of MUSE cells, exosomes, and Very Small Embryonic Like Stem Cells. Basic science of both PRP and stem cells are discussed. This presentation defines what constitutes an effective PRP preparation. Myths concerning stem cells are dispelled. One myth is that mesenchymal stem cells are the most important stem cell. This was the initial interpretation of Dr. Arnold Caplan the father of mesenchymal stem cell science. Dr. Caplan now feels that MSCs have an immunomodulation capacity which may have a more profound and immediate effect on joint chemistry and biology. We now learn in the talk that the hematopoietic stem cells are the drivers of tissue regeneration. Also discussed are adjuncts used which enhance the results. These therapies include supplements, LED therapy, lasers, electrical stimulation, and cytokine therapy. The scientific rationale is presented for each of these entities as to how they have a direct on stem cells.

Biography:

Haval Shirwan is Dr. Michael and Joan Hamilton Endowed Chair in Autoimmune Disease, Professor of Microbiology and Immunology, Director of Molecular Immunomodulation Program at the Institute for Cellular Therapeutics. He conducted his Graduate studies at the University of California in Santa Barbara, CA, and Postdoctoral studies at California Institute of Technology in Pasadena, CA. He joined the University of Louisville in 1998 after holding academic appointments at various academic institutions in the United States. His research focuses on the modulation of immune system for the treatment of immune-based diseases with particular focus on type 1 diabetes, transplantation, and development of prophylactic and therapeutic vaccines against cancer and infectious diseases. He is an inventor on over a dozen of worldwide patents, founder and CEO/CSO of FasCure Therapeutics, LLC, widely published, organized and lectured at numerous national/international conferences, served on study sections for various federal and non-profit funding agencies, and is on the Editorial Board of a dozen of scientific journals. He is member of several national and international societies and recipient of various awards.

Abstract:

We have recently shown that pancreatic islets engineered to display on their surface a novel form of FasL induce robust allotolerance. Tolerance is initiated by direct targeting of alloreactive pathogenic T effector cells with upregulated expression of Fas receptor for physical elimination through activation-induced cell death. The apoptotic process initiates a cascade of immunoregulatory mechanisms that involve phagocytes, TGF-β, and CD4+CD25+FoxP3+ Treg cells. Treg cells are not only critical to the induction but also maintenance of tolerance. This talk will focus on extensive discussion of these mechanisms and implication of this novel immunomodulatory approach for altering the balance between T effector and Treg cells with potential application to graft rejection and autoimmune diseases where a favorable balance for Treg cells has therapeutic potential.

Biography:

Julie Murrell is a Senior R&D Manager for Stem Cell Biology and Collaborations at EMD Millipore. Dr. Murrell has led an early technology assessment group for the past 7 years and has been part of the Stem Cell group for 3 years. Through that time, she has led the efforts to establish robust assays and identify new targets as key quality attributes for large scale stem cell manufacturing, with a special focus on hMSCs. Dr. Murrell’s background is in Cell and Molecular Biology. Her multi-disciplinary background has led to innovative team-driven approaches in the field of stem cell production.

Abstract:

As innovators move closer to clinical success, a gap in the ability to cost effectively manufacture cell therapies has been identified. To address this gap, we have demonstrated the use of single-use expansion and harvest systems that robustly expand and recover a variety of stem cells. An additional contributor to the system is the inclusion of high quality reagents that are animal origin free, lead to better yields and are supplied with a strong regulatory dossier. We will present data regarding ease of use, yield, viability and characterization for full solution expansion and harvest of manufactured cell therapies. Start to finish solutions for expansion and harvest are key enabling technologies for success in commercializing cell therapies.

Biography:

Professor Min Fang got her Ph.D from the Institute of Genetics and Developmental Biology, CAS in 2003. She got her postdoc training in Fox Chase Cancer Center in USA mainly on studying the pathogenesis of viral infection, as well as the mechanisms by which vaccines afford protection. She joined the Institute of Microbiology, CAS in June, 2012 as a professor supported by “Thousand Young Talents Program” of the China’s government. Her work was published in esteemed journals such as: Immunity, J Exp Med, PNAS, Plos Pathogen, etc, and multiply works were selected and referred by the “Faculty of 1000”.

Abstract:

Natural killer (NK) cells are bone marrow-derived lymphocytes crucial for host defense against several infections and cancer. We have previously shown that compared to young, aged C57BL/6 mice have decreased numbers of mature NK cells, resulting in susceptibility to mousepox, a lethal disease caused by ectromelia virus. We also found that the natural killer cell dysfunction of aged mice is due to the bone marrow stroma, not NK cell intrinsic. To investigate the melocular mechanisms that regulat the defective NK cell development in aged mice, we used high throughput sequencing to compare the gene expression differences between young and aged NK cells. We found that over 300 genes were differentially expressed in the aged NK cells compared to the youngs. Further identification of the main or check point regulators will shed new lights on the regulation of NK cell development in the aging enviroment.

Biography:

Paul Davis is Professor of Medicine at Albany Medical College and former Chair of the Department of Medicine at that institution. He has co-authored 250 publications, most of which deal with thyroid hormone actions. Shaker Mousa is Executive Vice President and Chair, Pharmaceutical Research Institute of the Albany College of Pharmacy and Health Sciences. He was a Principal Research Scientist at DuPont. He has co-authored 600 publications. Hung-Yun Lin is Professor in the Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University. Drs. Mousa, Lin and Davis have collaborated in studies of nongenomic actions of thyroid hormone and tetraiodothyroacetic acid (tetrac) and NDAT.

Abstract:

The PD-1 (programmed death-1)/PD-L1 (PD-ligand 1) checkpoint is a critical regulator of activated T cell-cancer cell interactions, serving to defend tumor cells against host immune destruction. Nano-diamino-tetrac (NDAT; Nanotetrac) is an anticancer/anti-angiogenic agent targeted to the thyroid hormone-tetrac receptor on the extracellular domain of integrin αvβ3. NDAT inhibits the cancer cell PI3-K and MAPK signal transduction pathways that are critical to PD-L1 gene expression. We examined actions in vitro of thyroid hormone (L-thyroxine, T4) and NDAT on PD-L1 mRNA abundance (qPCR) and PD-L1 protein content in human breast cancer (MDA-MB-231) cells and colon carcinoma (HCT116 and HT-29) cells. In MDA-MB-231 cells, a physiological concentration of T4 (10-7 M total; 10-10 M free hormone) stimulated PD-L1 gene expression by 38% and increased PD-L1 protein by 2.7-fold (p<0.05, all changes). NDAT (10-7 M) reduced PD-L1 in T4-exposed cells by 21% (mRNA) and 39% (protein) (p<0.05, all changes). In HCT116 cells, T4 enhanced PD-L1 gene expression by 17% and protein content by 24% (p<0.05). NDAT reduced basal PD-L1 mRNA by 35% and protein by 31% and in T4-treated cells lowered mRNA by 33% and protein by 66%. In HT-29 cells, T4 increased PD-L1 mRNA by 62% and protein by 27%. NDAT lowered basal and T4-stimulated responses in PD-L1 mRNA and protein by 35-40% (p<0.05). Activation of ERK1/2 was involved in T4-induced PD-L1 accumulation. We propose that, by a nongenomic mechanism, endogenous T4 may clinically support activity of the defensive PD-1/PD-L1 checkpoint in tumor cells. NDAT non-immunologically suppresses basal and T4-induced PD-L1 gene expression in cancer cells.

Biography:

Abstract:

Recent discoveries using organoid 3D culture systems under quite economic conditions demonstrated the inherent potential of pluripotent stem cells and in some cases even adult progenitor stem cells for reproducible complex self-organization. Although efforts have been made trying to explain some of the observed phenomena in terms of classical developmental mechanisms, such as, cell sorting, morphogen mediated patterning and cell morphogenesis; the accurate mechanisms underlying the precise organization of tissue like complexity are largely unknown. One striking feature of Small Mobile Stem cell (SMS) capacity to self-organization is its proclivity to generate a multitude of highly diverse complex geometric shapes, in an economic simple in vitro set up. These shapes create among other things 3D topographic micro-patterns. Similar patterns have been widely recognized to participate in controlling cellular functions such as cell adhesion, migration, proliferation, and differentiation. It is quite possible that these, largely unrecognized SMS derived structures, represent a fundamental missing link to the overall organization of other cells and tissues at large. Specifically adult SMS cells are capable to interact dominantly with other commonly known cells, and could therefore be able to provide for the preeminent scaffolding, that is essential for cell guidance into various tissue spatial organizations.

Biography:

earned my PhD degree from the University of Bradford, UK as an awardee of Chancellor Cancer Research Studentship- A collaborative PhD scholarship offered by University of Bradford, UK and SKMCH&RC, Pakistan. I aim to establish my career in cancer research in Pakistan. Oral cancer incidence is high in this part of world because of various life style choices. My research study is first attempt in Pakistan to study this disease using mass spectrometry. The pilot study was initiated in April 2013 using facilities at Basic Sciences Research Laboratory, SKMCH&RC and Institute of Cancer Therapeutics, University of Bradford, UK. This is an ongoing project and has been published in peer reviewed international journals (Cancer Cell International, 2014) and presented as posters in international meetings (BSPR meeting UK, 2015).

Abstract:

Recently a sub-population of cells with stem cell characteristics, reported to be associated with initiation, growth, spread and recurrence, has been identified in several solid tumors including oral tongue squamous cell carcinoma (OTSCC). The aim of our pilot study was to isolate CD44+cancer stem cells from primary cultures of OTSCC and neck node Level I (node-I) biopsies, grow cell spheres and observe their characteristics in primary cultures. Parallel cultures of hyperplastic lesions of tongue (non-cancer) were set up as a control. Immunohistochemistry was used to detect CD44/CD24 expression and magnetic activated cell sorting to isolate CD44+ cell populations followed by primary cell culturing. Both OTSCC and node-I biopsies produced floating spheres in suspension, however those grown in hyperplastic and node-I primary cultures did not exhibit selfrenewal properties. Lymph node metastatic OTSCC, express higher CD44/CD24 levels, produce cancer cell spheres in larger number and rapidly (24 hours) compared to node negative OTSCC (1 week) and non-cancer specimens (3 weeks). In addition, metastatic OTSCC have the capacity for proliferation for up to three generations in primary culture. This in vitro system will be used to study cancer stem cell behavior, therapeutic drug screening and optimization of radiation dose for elimination of resistant cancer cells.

Biography:

I am dr seyed amir mousavi a licensed dentist with Post graduate education in Endodontics. I have research since 2007, and have trained multiple undergraduate students in Isfahan dental faculty. My DDS thesis was Isolation of stem cell from human exfoliated primary teeth.in my thesis we show that we can isolate stem cells from dental pulp of primary teeth and then we can differentiate these cells to other special cells like adipocyte. My MS thesis was Effect of topical dexamethasone on histologic response of human dental pulp to one step MTA direct pulp capping and partial pulpotomy: A randomized clinical trial.I have 4 publications in journals and 7 oral and poster presentations in international congresses. I still have interest in stem cells research.

Abstract:

Introduction: Finding an accessible resource is an important goal for stem-cell research. The aim of this study is to isolate the stem cells from dental pulp of deciduous teeth. Method and material: Anterior deciduous teeth from children 6 to 9 years old which were exfoliating normally were used in this experiment. The exfoliated teeth were immediately placed in a normal saline sterile solution containing antibiotics and were kept in 4 C. The dental pulp was isolated in complete sterile condition and then divided into small pieces with a fine scalpel. Then it was put on 4 mg/ml collagenase type 1 for one hour at 37 c for preparation of single cell suspention. The samples have been cultured in MEMenvironment. To prove that these cells are stem cells we used flow cytometry. Results: 1- Rest of pulp of deciduous teeth contains a population of fibroblast like cells. 2-SHED (stem cells from human exfoliated deciduous teeth) show positive response toward CD90 as an excellent mesenchymal marker and show negative response toward CD31 as an endothelial marker. 3- The rate of reproduction in these stem cells was high. 4- SHED has an ability to differentiate into adipocytes andosteocytes. Conclusion: The deciduous teeth can be used as an accessible and great resource of stem cells without having any moral problems in researches involving tissue engineering.