Geometrical guidance of stem cell fate : elucidation studies and implication in tissue engineering
Tay, Chor Yong
Date of Issue2012
School of Materials Science and Engineering
Tissue engineering and regenerative medicine aims to construct functional tissues replacement through precise control of local environment that promotes proliferation and differentiation of cells. Widespread attention has been focused on using stem cells as the primary source for tissue engineering due to its self-renewal capability and multipotency. Stem cells are highly responsive to the microenvironment signals and given the right condition, it is possible to direct stem cell differentiation into a particular cell type in the body. Recent findings have underscored the important role of mechanical environment in directing stem cell lineage commitment. For instance it has been shown that materials compliance, applied mechanical stimulus (e.g. stretch, strain, and shear) and regulation of cell shape can exert significant influences in regulating tissue specific gene expression and protein translation. The objective of this project is to employ a simple and versatile technique to control the spatial arrangement, orientation and geometry of stem cell for the purpose of elucidating the basis of cell shape distortion, cytoskeleton rearrangement and focal adhesions distribution on bone marrow derived human mesenchymal stem cells (hMSCs) lineage commitment in the absence of exogenous soluble factors. To achieve this, microcontact printing was employed to control cell spreading on extracellular matrix protein defined regions. It was found that hMSCs cultured on 20μm wide fibronectin lanes printed on poly (lactide-co-glycolide) substrate adopted a highly elongated morphology with concomitant upregulation of myogenic mRNA transcripts and protein, indicative of muscle differentiation. Further elucidation studies revealed that repression of the FAK-ERK signaling events may serve as a molecular basis for the cell shape induced muscle lineage commitment hMSCs.