PREDICTIVE MODELING AND BIOMECHANICAL MICROENGINEERING OF MESENCHYMAL STEM CELLS: A HIGH CONTENT SCREENING PLATFORM TO ENHANCE LINEAGE SPECIFIC DIFFERENTIATION

摘要

A systematic approach was established to account for dynamic cellular remodeling during MSC differentiation. Quantitative measurements of multiple parameters allowed us to engineer advanced computational methods to analyze and predict the changes in differentiating MSCs. Perhaps most significant was a consistent pattern observed in all types of MSC differentiation at the single-cell level: the cytoskeleton significantly reorganized before lineage-specific cellular changes occurred (in the case of adipogenic differentiation, the cytoskeleton reorganized before lipid accumulation). The single-cell/multicellular biomimetic microenvironments significantly enhanced MSC differentiation, further demonstrating the vast role cellular mechanics play in stem cell differentiation. This innovative platform of stem cell differentiation (automated/predictive HCS and biomimetic microengineering) will soon be extended to other types of stem cells (e.g., induced pluripotent stem cells, mouse embryonic stem cells, hematopoietic stem cells, neural stem cells, etc).