Mon-Juan Lee has completed her MS degree in Chemical Engineering in 2000 and PhD degree in Life Science in 2006 from National Tsing Hua University, Hsinchu, Taiwan. She is currently an Associate Professor of the Department of Bioscience Technology with joint affiliation in the Graduate Institute of Medical Sciences at Chang Jung Christian University, Tainan, Taiwan. Her research interests include stem cell and bone biology, nanobiotechnology, as well as LC-based biomedical applications.
Sclerostin, a secreted glycoprotein expressed predominantly in osteocytes that inhibits bone formation by antagonizing the Wnt/β-catenin signaling pathway, is considered a new target for the treatment of osteoporosis. We devised a novel aptamer-based competitive drug screening platform for small-molecule sclerostin inhibitors from libraries of biologically active chemical compounds to facilitate drug repurposing and drug discovery for osteoporosis. Baicalein, a flavonoid and alizarin, an anthraquinone, are two of the potential sclerostin inhibitors obtained from the aptamer-based competitive assay and verified by an antibody-based competitive assay. The osteogenic potential of baicalein and alizarin was assessed by their capability to suppress the protein expression of sclerostin and to stimulate alkaline phosphatase activity. When mouse bone cell line IDG-SW3 was treated with baicalein or alizarin prepared in osteogenic induction medium, protein expression of sclerostin decreased compared to cells incubated in proliferation medium and osteogenic induction medium. In the presence of baicalein or alizarin, osteogenic differentiation was accelerated in human fetal osteoblasts hFOB1.19, in which higher alkaline phosphatase activity was detected than the control and cells treated only with osteogenic induction medium. Potential small-molecule drug candidates obtained in this study is expected to provide new therapeutics, as well as more insights into the structure–activity relationship of sclerostin inhibitors for further rational drug design. The common features in the chemical structure of baicalein and alizarin and their osteogenic potential demonstrated in this study suggest that flavonoids and anthraquinones may serve as lead compounds of small-molecule inhibitors of sclerostin for the development of bonestimulating new drugs.
Milla Lampinen has received her PhD from University of Helsinki in 2003 from Prof. Kari Keinänen’s lab, studying glutamate receptor ligand binding determinants. She has completed her Post-doctoral training from Prof. Anu Wartiovaara’s group studying mitochondrial disease and at Finnish Red Cross Research and development unit, studying stem cells and product applications thereof. She is currently working on stem cell behavior and cardiac stem cell therapy studies in Dr. Esko Kankuri’s group at University of Helsinki.
The loss of cardiac myocytes and the nonreversible decrease in cardiac output are the major challenges of ischemic myocardial injury (MI) and chronic heart failure (HF). Recent studies indicate that cardiac-derived cells offers new potential to repair myocardium with sustained functional benefit. We present here a novel, cost-effective cell-patch method, to non-invasively harvest AA cell-micrograft from surgical left-over tissue of CABG and to deliver them within scaffold to provide easy epicardial targeting and intraoperative treatment of HF. We applied the cellular therapy protocol both in mouse acute MI-model and in human safety-feasibility trial. In mouse, allogeneic mouse AA-cells containing scaffold are place on infarction area. For eight weeks echocardiographic follow-up, the cell-on-scaffold treatment showed statistically higher functional recovery in under curve-analysis of left ventricle ejection fraction (LVEF) than the empty-scaffold and non-treated infarction. Also, remodeling was significantly reduced by scaffold+/-cells, measured by the larger relative wall thickness of the stained collagen in nontreated group. The highest tissue expression of HF identifier, natriuretic peptide, in infarction group further suggests the AA-cell therapy’s beneficial effect on heart survival, while empty-scaffold may also provide structural support to ventricle wall. In clinical safety trial, six patients undergoing elective CABG are treated with diameter of 2.5cm cell-on-scaffold. In follow-up of first patient at three months, magnetic resonance imaging revealed good performance of the heart and visible thickened ventricle wall in comparison to pre-operative analysis. The patient’s generally good recovery from the operation further suggests that the protocol is feasible for operation room use and the cell-micrograft therapy is safe.