11^th World Congress and Expo on Cell & Stem Cell Research March 25-26, 2019 Hong Kong, China

Biography:

Paul J Davis obtained the MD degree at Harvard Medical School and had his internal medicine clinical and endocrine research training, respectively, at Albert Einstein College of Medicine (NY) and the NIH. He has served in a number of senior administrative positions in academic institutions and in national societies. His research is focused on the molecular mechanisms of thyroid hormone actions. He has co-authored 275 research publications and 40 textbook chapters; he has co-edited four textbooks. He and colleague SA Mousa described the cell surface receptor for thyroid hormone on integrin αvβ3. They also co-founded NanoPharmaceuticals LLC (Rensselaer, NY).

Abstract:

Integrin α_Vβ₃ is a structural protein of the plasma membrane that is generously expressed by cancer cells and dividing endothelial cells; until recently, important functions of the integrin have been seen to relate to cell-cell and cell-extracellular matrix protein interactions. The extracellular domain of αvβ₃ is now appreciated to contain a small molecule receptor for thyroid hormone, primarily, L-thyroxine (T4). From this cell surface hormone receptor, the expression of a large panel of cancer-relevant genes is differentially regulated by thyroid hormone analogues. These genes include multiple cell division regulating cyclins and HRAS and KRAS genes linked to uncontrolled cell division; KRAS is also related to cancer stem cell (CSC) maintenance and to tumor recurrence. Transcription of these genes is downregulated by P-bi-TAT, consisting of a thyroid hormone analogue, tetraiodothyroacetic acid (tetrac), chemically coupled to polyethylene glycol (PEG). IDH2 is involved in tumor cell mitochondrial metabolism; P-bi-TAT decreases IDH2 transcription, thus promoting apoptosis by the intrinsic (mitochondrial) pathway. Expression of ERBB2 is important to tumor cell invasiveness and metastasis and is downregulated by P-bi-TAT. The ERBB family of proteins is also important to tumor cell chemoresistance. αvβ3 regulates via the thyroid hormone receptor the transcription of ABCB1, whose gene product—the P-glycoprotein of the plasma membrane—exports a number of chemotherapeutic agents from tumor cells as a component of chemoresistance. Expression of pro-angiogenic VEGFA, bFGF and PDGF genes is also decreased by P-bi-TAT action at αvβ₃, as is the EGFR gene whose transcription is important to angiogenesis and tumor cell proliferation. Matrix metalloproteinase (MMP) gene expression is critical to cell migration/metastasis and to angiogenesis; P-bi-TAT induces a signal at the integrin to reduce MMP production. The EGFR protein is a tyrosine kinase and thus P-bi-TAT, by downregulating expression of EGFR, functions as a tumor cell-relevant tyrosine kinase inhibitor (TKI). Another TKI gene affected by P-bi-TAT is KIT. This complex set of actions of P-bi-TAT on gene expression implies that T4 may act on tumor cell αvβ₃ to support, rather than inhibit, the expression of these genes whose products are linked to tumor cell survival. We have shown that T4 via αvβ3 does stimulate expression of VEGFA and bFGF, of MMPs, ABCB1 in tumor cells. Transduction of thyroid hormone and hormone analogue signals downstream of αvβ₃ is a function of MAPK/ERK1/2 and PI3K, the genes and enzyme activities of which are regulated by thyroid hormone. These observations indicate that the importance of αvβ₃ to cancer cell function and survival also includes the actions of thyroid hormone analogues on the integrin.

Biography:

Keating received her Bachelors of Science degree in Chemistry from the University of Wisconsin, Madison and her PhD in Chemistry from the University of California, Davis. She was a Postdoctoral Fellow at Emory University and at Pacific Northwest National laboratory. She has worked as an analytical and physical chemist at AT&T BellLaboratories, Wyeth, and the University of Illinois, specializing in NMR spectroscopy of proteins and small molecules. Dr. Keating transitioned to scientific editing in 2009 and currently is Science Editor/Medical Writer at the Pharmaceutical Research Institute at the Albany College of Pharmacy and  Health Sciences in Rensselaer, NY.

Abstract:

Integrin α_Vβ₃ is a structural protein of the plasma membrane that is generously expressed by cancer cells and dividing endothelial cells; until recently, important functions of the integrin have been seen to relate to cell-cell and cell-extracellular matrix protein interactions. The extracellular domain of αvβ₃ is now appreciated to contain a small molecule receptor for thyroid hormone, primarily, L-thyroxine (T4). From this cell surface hormone receptor, the expression of a large panel of cancer-relevant genes is differentially regulated by thyroid hormone analogues. These genes include multiple cell division regulating cyclins and HRAS and KRAS genes linked to uncontrolled cell division; KRAS is also related to cancer stem cell (CSC) maintenance and to tumor recurrence. Transcription of these genes is downregulated by P-bi-TAT, consisting of a thyroid hormone analogue, tetraiodothyroacetic acid (tetrac), chemically coupled to polyethylene glycol (PEG). IDH2 is involved in tumor cell mitochondrial metabolism; P-bi-TAT decreases IDH2 transcription, thus promoting apoptosis by the intrinsic (mitochondrial) pathway. Expression of ERBB2 is important to tumor cell invasiveness and metastasis and is downregulated by P-bi-TAT. The ERBB family of proteins is also important to tumor cell chemoresistance. αvβ3 regulates via the thyroid hormone receptor the transcription of ABCB1, whose gene product—the P-glycoprotein of the plasma membrane—exports a number of chemotherapeutic agents from tumor cells as a component of chemoresistance. Expression of pro-angiogenic VEGFA, bFGF and PDGF genes is also decreased by P-bi-TAT action at αvβ₃, as is the EGFR gene whose transcription is important to angiogenesis and tumor cell proliferation. Matrix metalloproteinase (MMP) gene expression is critical to cell migration/metastasis and to angiogenesis; P-bi-TAT induces a signal at the integrin to reduce MMP production. The EGFR protein is a tyrosine kinase and thus P-bi-TAT, by downregulating expression of EGFR, functions as a tumor cell-relevant tyrosine kinase inhibitor (TKI). Another TKI gene affected by P-bi-TAT is KIT. This complex set of actions of P-bi-TAT on gene expression implies that T4 may act on tumor cell αvβ₃ to support, rather than inhibit, the expression of these genes whose products are linked to tumor cell survival. We have shown that T4 via αvβ3 does stimulate expression of VEGFA and bFGF, of MMPs, ABCB1 in tumor cells. Transduction of thyroid hormone and hormone analogue signals downstream of αvβ₃ is a function of MAPK/ERK1/2 and PI3K, the genes and enzyme activities of which are regulated by thyroid hormone. These observations indicate that the importance of αvβ₃ to cancer cell function and survival also includes the actions of thyroid hormone analogues on the integrin.

Biography:

Diana Anderson (H index 62) holds the Established Chair in Biomedical Sciences at the University of Bradford. She obtained her first degree in the University of Wales and second degrees in the Faculty of Medicine, University of Manchester. She has 500+ peer-reviewed papers, 10 books, has successfully supervised 32 PhDs, is an Editorial Board Member of 10 international journals. She is Editor-in-Chief of a book series on Toxicology for the Royal Society of Chemistry. She gives plenary and key note addresses at various international meetings. She is a consultant for many international organizations, including WHO, EU, NATO, TWAS, UNIDO, OECD.

Abstract:

Germline stem cells are susceptible to anticancer drug induced-DNA damage and oxidative stress, and even low doses to the testicular cells may pose reproductive risks with possible treatment-related infertility. DNA damage in spermatogonial stem cells, caused by chemotherapy, could induce cell cycle arrest and germ cell apoptosis, with the potential to cause infertility in men. Spermatogonial stem cells are the only cell type capable of transmitting genetic information to future generations. Various compounds have a negative impact on the germline stem cells, either directly, or indirectly affecting them through their action on the spermatogonial cells. Eventually, these effects can inhibit fertility, and may have toxic consequences for the progress of the progeny. Oxaliplatin is a platinum-based anti-cancer drug with antineoplastic properties used mainly for colorectal cancer. It is cytotoxic due to platinum binding to DNA and the formation of intrastrand cross-links between neighbouring guanines. To examine the effects of oxaliplatin on spermatogonial cells separated using STAPUT unit-gravity velocity sedimentation. DNA damage was assessed in the Comet assay. The effects of oxaliplatin on mRNA and their proteins of P53, P21 and BLC2 were also studied using quantitative polymerase chain reaction (qPCR) and Western blot methods. Results indicated that oxaliplatin induced DNA damage and significantly increased levels of P53, P21 and decreased BLC2 mRNA and their proteins.

Understanding the mechanisms of action of oxaliplatin in spermatogonial stem cells is an important way to examine emerging new protection strategies for the reproductive system.

Biography:

Aibing Wang obtained BS and MS from Hunan Agricultural University (HUNAU) in 1998 and 2001, respectively; PhD majored in Biochemistry and Molecular Biology from Peking Union Medical College (PUMC) in 2005. He was a Visting and Research Fellow in National Heart, Lung and Blood Institute (NHLBI) of National Institutes of Health (NIH) during 2005-2011. He worked as a Biologist and Senior Biologist in NIH during 2011-2016; He joined in CVpath Insitute Inc as a Senior Scientist in 2016; Currently, he is a Professor of Molecular biology and virology in the School of Veterinary Medicine of Hunan Agricultural Univesity since 2016. He has obtained 3 awards from NIH and 3 grants from the Chinese government, applied for 3 patents and published 45 peer-reviewed publications. His current research interests mainly include: investigating the gene functions or molecular mechanisms associated with virus infection and other diseases; exploring the development of virus detection and vaccine using cutting-edge technologies such as CRISPR/Cas9.

Abstract:

Targeted integration of exogenous genes into so-called safe harbors/friend sites, offers the advantages of expressing normal levels of target genes and preventing potentially adverse effects on endogenous genes. However, the ideal genomic loci for this purpose remain limited. Additionally, due to the inherent and unresolved issues with the current genome editing tools, traditional embryonic stem (ES) cell-based targeted transgenesis technology is still preferred in practical applications. Here, we report that a high and repeatable homologous recombination (HR) frequency (>95%) is achieved when an approximate 6kb DNA sequence flanking the MYH9 gene exon 2 site is used to create the homology arms for the knockout/knock-in of diverse nonmuscle myosin II (NM II) isoforms in mouse ES cells. The easily obtained ES clones greatly facilitated the generation of multiple NM II genetic replacement mouse models, as characterized previously. Further investigation demonstrated that though the targeted integration site for exogenous genes is shifted to MYH9 intron 2 (about 500bp downstream exon 2), the high HR efficiency and the endogenous MYH9 gene integrity are not only preserved, but the expected expression of the inserted gene(s) is observed in a pre-designed set of experiments conducted in mouse ES cells. Importantly, we confirmed that the expression and normal function of the endogenous MYH9 gene is not affected by the insertion of the exogenous gene in these cases. Therefore, these findings suggest that like the commonly used ROSA26 site, the MYH9 gene locus may be considered a new safe harbor for high-efficiency targeted transgenesis and for biomedical applications.

Biography:

Lin received his PhD degree at SUNY Buffalo in 1991. Dr. Lin has served at the VA Hospital and Ordway Research Institute in Albany, NY as a senior scientist. Later, he worked at the Pharmaceutical research Institute (PRI) at the Albany College of Pharmacy and Health Sciences, Albany, NY. Dr. Lin joined Taipei Medical University as full professor in 2012. For the past three years, his research has focused on mechanisms involved in thyroidhormone-induced pathogenesis in colorectal cancer and other types of cancers.

Abstract:

The checkpoint programmed cell death protein 1 (PD-1)/ programmed death-ligand 1(PD-L1) plays an important role in cancer proliferation. Thyroid hormone, L-thyroxine (T4), induces the expression of PD-L1 and promotes cell proliferation in cancer cells. Resveratrol inducesanti-proliferation in various types of cancer cells via binding to integrin αvβ3 to increase nuclear inducible cyclooxygenase (COX)-2 accumulation, complex with p53, and induce p53-dependent anti-proliferation. We investigated the mechanism by which L-thyroxine impairs resveratrolinduced anti-proliferation in human cancer cells. L-thyroxine increased expression and cytoplasmic accumulation of PD-L1. The increased PD-L1 retained  resveratrol-induced COX- 2 in cytoplasm and prevented COX-2 nuclear accumulation. Byinhibiting activated PI-3K-STAT3 signal transduction axis by thyroid hormone, anodiamino-tetrac (NDAT) was able to inhibit thyroid hormone-induced PD-L1 and relieved the inhibitory effect of L-thyroxine on resveratrolinduced nuclear accumulation of COX-2. DAT is a thyroid hormone derivative. The NDAT-inhibited consequences were re-establishingCOX-2/p53-dependent gene expression and anti-proliferation. These findings provide new insights into the antagonizing effect of NDAT on L-thyroxineinduced interference withresveratrol-induced anticancer properties.

Biography:

Lucero Alvarado has done her B.S from The University of Texas at San Antonio 2014, she is currently pursuing her M.S. from the University of Texas at San Antonio (2017). Her research  interests is developing cell –based products for use in combat casualty care and healthcare settings. She has three years experience in manurfacturing cell-derived extra-cellular matrices in a GMP setting at the San Antonio based biotechnology company, StemBioSys, Inc. Published in Stem Cell Research and Therapy and presented at RegenMed SA conference in San Antonio, TX

Abstract:

Acute Respiratory Distress Syndrome (ARDS) is a form of acute lung injury that causes morbidity and mortality in ill patients. Current therapies for ARDS include lung protective ventilation and fluid clearance, but do not treat the underlying cause. Mesenchymal stem cells (MSCs) have been proposed as a promising form of therapy to treat ARDS. Currently, it is unknown which MSC type is best-suited to treat ARDS. The goals of these study were therefore three-fold: 1. Create a model of ARDS in vitro; 2.Identify which MSC source, bone marrow (BM) or adipose (AD)-MSC, is more suitable to treat ARDS; and 3. Evaluate the ability of MSCs to mitigate the ARDS-like injury.

To accomplish this, we utlized injurious signals typically manifested in ARDS, such as low oxygen concentration (i.e., hypoxia) and lipopolysaccharide (LPS). LPS is a bacterial endotoxin that induces ARDS in vivo and mimics infection in vitro. We then subjected a co-culture system of lung epithelial and endothelial cells to these signals to induce the injury. Finally, we added MSCs to this sustem to evaluate their ability to mitigate the injury.

After subjecting the co-culture system to hypoxia and LPS, we observed an increase in apoptosis as evidenced by increase in mitochondrial membrane potential and Annexin V analysis. In comparing MSC types, both BM-MSCs and AD-MSCs suppressed T-cell proliferation in a mixed lymphocyte reaction assay; however, AD-MSCs were more potent following a LPS challenge. Additionally, both cell types diminished the secretion of the pro-inflammatory cytokines IFN-γ, IL-13, IL-1α, and IL-1β; yet, unlike BM-MSCs, AD-MSCs showed a significant increase in the anti-inflammatory IL-1RA after LPS exposure. Following the addition of AD-MSCS, there was a significant decrease in protein pearmeability in the co-culture system.

Taken together, in the co-culture system, we successfully established a injurios environment rmimicking an ARDS-like condition. Compared to BM-MSCs, AD-MSCs appear to be a more suitable candidate for ARDS due to their superior anti-inflammatory function.  Therefore, Addition of AD-MSCs to an in vitro co-culture system of ARDS mitigated the injury as evidenced by reduction in membrane permeability.

Biography:

Abstract:

Background: In the last few decades, thousands of patients have benefited from platelet-rich plasma (PRP) therapies, emerging as a safe alternative in many different medical fields. The use of Platelet-Rich Plasma (PRP) in medicine has become increasingly more widespread during the last decade. Eczema (atopic dermatitis) is a complex disorder caused by the interplay between multiple genetic and environmental factors. Particularly in patients with severe disease, the effect is not just an itchy rash but also the secondary effects on the psychological well-being of the patient and their carers, particularly disturbed sleep. The aim of the study was to treat the patient by using the platelet-rich plasma.

Materials and Methods: 15cc blood sample was collected from the patient. The baseline parameters included complete blood count (CBC), erythrocyte sedimentation rate(ESR), fasting blood sugar/ransom blood sugar(FBS/RBS), urea, creatinine and uric acid, We also checked for the inflammation by performing C-Reactive Protein(CRP) and immunoglobulin IgE for the allergy. The rest of the blood sample was used for the PRP.The platelet-rich plasma (PRP) was collected with the help of spiral needle in sterilized falcon tube which was then place in Adilight 2 for the activation of PRP for 15minutes.

Result: In baseline reports, it was noted that eosinophil was elevated, with ESR. The sugar level, urea, creatinine and Uric acid were at the normal range. The CRP was high and igE was abnormal. She underwent three consecutive platelet-rich plasma therapy with a gap of 15 days in between. We assessed the patients by taking the photograph and repeating the parameters which were elevated before the second and third treatment. After the first therapy, the images showed improvement. However, after the second therapy, the patient reported marked control on the itchy and disappearance of rash. She was quite satisfied with the treatment because of the treatment she was taking increasing the rashes.

Conclusion: This study suggests the use of platelet-rich plasma has a beneficial effect on skin diseases and can thus be attributed to various platelet-derived growth factors causing improvement in the function on skin and promotion to decrease the rashes and itching. It is safe, cheap and non-allergic and it appears to be a useful adjuvant in the management of eczema.

Biography:

Moses Kayongo holds a Masters and a Doctorate in Public Health (DrPH) has expertise in Preventive Health Care. He is currently working as Assistant Professor at University of Lay Adventists of Kigali (UNILAK) and Adventist University of Central Africa (AUCA) as an adjunct Lecturer teaching public health courses and research methodology. He has a research interest in self-care management of Noncommunicable diseases however after his Doctoral studies’ completion, his second child was diagnosed at 5years with sickle cell disease and suffered several strokes. Given his educational background, he developed a research interest in Sickle Cell self-care management and has since developed and supported several awareness programs for parents of children with sickle cell disease.

Abstract:

Statement of the Problem: Haplo Identical Stem Cell Transplant (SCT) procedure  in some countries is still considered experimental and performed only as part of research studies because of the complications during and after the transplant such as high risk for infections, Graft-versus-host disease (GVHD), Graft failure, Nutrition problem, Low blood counts, dermatological challenges, Social and emotional concerns and others. The number of Haplo Identical SCT procedures nonetheless, continues to rise as parents in many African countries seek treatment for the increasing diagnosis of sickle cell disease among children. Parents as caregivers are destined to face a greater number of challenges yet there has not been any documented shared experience of this specific procedure. The purpose of this study report is to describe the 2year caregiving experience and challenges by a family living in Rwanda, since their nine-year-old daughter’s Post Haplo-identical SCT, done on (December 28^th, 2016) at Christian Medical College Hospital, Vellore, India to further the understanding and knowledge of the caregiving aspects of this procedure.

Methodology/Finding: Using a case report approach, six key points emerge from a caregiving perspective of parents’ experiences and challenges namely: nutritional adjustments, continuous home monitoring and evaluation of the child’s general wellbeing, compliance to routine consultation / medications, father’s direct involvement and social interaction difficulties besides the mother’s role.

Conclusion: Despite this procedure being delicate and complex during and after transplant, our experience as caregivers has shown that Pre/Post-Haploidentical SCT orientation and existing experienced doctors in the different specialties’ related to the complications have so far greatly contributed to our post-transplant adaptation to care to give.