Invited Paper BI-WeM9
Engineering Stem Cell Differentiation via Material Properties

Wednesday, November 2, 2011, 10:40 am, Room 108

Stem cell differentiation is sensitive to a variety of global and local environmental cues that impact cell fate decisions. Pluripotent stem cells (i.e. ESCs & iPSCs) are capable of recapitulating many aspects of early development and can serve as a robust cell source for the development of cell-based diagnostics and regenerative medicine therapies. ESCs are commonly differentiated as three-dimensional multi-cellular aggregates referred to as “embryoid bodies” (EBs), because of their ability to mimic the early morphogenic transformation of pluripotent cells into derivatives of the three germ lineages (ecto-, endo-, and mesoderm). In order to better understand and ultimately control ESC morphogenesis, w e have focused on systematically engineering biochemical and biophysical parameters of the 3D EB microenvironment via the integration of different biomaterials and examining the emergent results on stem cell differentiation. Microparticles (MPs) of varying size (1-20 µm) and chemistries (i.e. PLGA, agarose, gelatin) were incorporated within 3D stem cell aggregates in a dose-dependent manner (~1 particle / 10 cells) without adversely affecting cell viability. Interestingly, the mere presence of relatively small numbers of different types of materials alone could modulate stem cell phenotype as evidenced by gene expression profiling and immunophenotype analyses. D elivery of morphogenic factors, such as retinoic acid (RA), bone morphogenic protein 4 (BMP4) or vascular endothelial growth factor (VEGF), to ESCs from incorporated MPs significantly impacted the differentiation of the cells to different lineages and was more efficient than comparable soluble treatment methods. Altogether these results suggest that engineered biomaterials can direct the differentiation of stem cells through modulation of biochemical and/or biophysical properties of the 3D microenvironment. It is expected that the development of inherently scalable techniques to direct pluripotent stem cell differentiation will benefit the biomanufacturing of stem cell derivatives for regenerative cellular therapies and in vitro cell based diagnostic technologies, as well as enable engineering of tissues directly from stem cells.