Engineering the Stem Cell Microenvironment
Overview - One of the primary challenges impeding the development of stem cell technologies is the inability to efficiently direct the differentiation of stem cells in a reproducible and scalable manner towards a desired cell phenotype. During development, cell fate decisions are spatially and temporally directed by the composition of the biochemical and mechanical properties of the extracellular stem cell microenvironment. Thus, we seek to recapitulate spatiotemporal controlled methods to present molecular cues to stem cells in order to more effectively and efficiently direct differentiation.
Microsphere incorporation - One way we are engineering the stem cell microenvironment is via the incorporation of biomaterial particles directly within aggregates of cells undergoing differentiation. The biomaterial particles, often in the form of microspheres, can be engineered to temporally control the presentation of morphogenic factors locally. Depending upon the choice of materials and morphogens, this approach can be broadly used to direct stem cells to various differentiated cell fates. We are working in collaboration with polymer chemists, biomaterials scientists and engineers to develop novel delivery vehicles and related technologies capable of improving the controlled presentation of morphogens to stem cells undergoing differentiation.
Hydrogel encapsulation - Another manner in which we are attempting to more homogeneously control stem cell fate is via the encapsulation of cells within 3D hydrogel materials. By varying the biochemical and mechanical properties of different hydrogel materials, specific cues can be more uniformly presented to large populations of stem cells simultaneously. In addition, cultivation and differentiation in 3D enables stem cells to cultivated at much higher densities than conventional 2D approaches, thereby potentially facilitating scalable production of cells for regenerative therapies or in vitro diagnostic technologies.