Harnessing the ability of stem cells to differentiate and contribute to tissue repair has enormous potential for wound healing, tissue regeneration, and reinstating the functionality of dysfunctional tissues/organs. However, the full potential of stem cells in regenerative medicine is currently limited by our ability to reproducibly culture them ex vivo and differentiate them in a controlled manner to the cell type of interest. A challenging prerequisite for overcoming such a limitation is to understand how the cell microenvironment regulates stem cell proliferation and differentiation. In our lab, we are developing a number of tools and technologies to understand and direct stem cell fate commitment.
Some of our ongoing studies are: (i) Developing synthetic matrices to support self-renewal of human pluripotent stem cells (hESCs and iPSCs) (Chang CW et al., "Engineering Cell-Material Interfaces for Long-term Expansion of Pluripotent Stem Cells." Biomaterials S0142-9612(12):1141-1146 (2012); Brafman, D.A., et al. "Long term human pluripotent stem cell self-renewal on synthetic polymer surfaces." Biomaterials, 31:9135-9144, (2010).
(ii) Developing strategies to direct myogenic differentiation of stem cells. Our studies show that PDGFRA+ cells derived from hESCs undergo myogenic commitment in vitro and in vivo. When transplanted in vivo into a physically injured skeletal muscle, the hESC-derived myogenic progenitor cells were engrafted into the host tissue. (Hwang et al., Directed In Vitro Myogenesis of Human Embryonic Stem Cells and Their In Vivo Engraftment” PLoS One).
In addition to the injury model, we are also investigating the potential of these hESC-derived progenitor cells to treat pathologies like Duchenne muscular dystrophy (DMD). (iii) Developing strategies to direct osteogenic differentiation of stem cells. We have shown that synthetic matrices containing calcium phosphate (CaP) minerals can direct osteogenic differentiation of hMSCs, hESCs, and iPSCs (Phadke et al., Mineralized Synthetic Matrices as an Instructive Microenvironment for Osteogenic Differentiation of Human Mesenchymal Stem Cels". Macromol. BioSci. 12(8):1022-1032 (2012)). (iv) We are also developing strategies to promote engraftment and function of transplanted stem cells and stem cell-derived progenitor cells.