Manipulating the stem cell microenvironment

We can use simple physical principals from nature as templates to manipulate the stem cell microenvironment. For example, molecular sequestering is driven by fundamental physical principles, and is also a common mechanism by which the extracellular matrix (ECM) locally regulates soluble growth factor concentrations. We have hypothesized that chemically well-defined cell culture environments can be used to develop ECM-mimicking (or “bioinspired”) ligands that influence stem cell behavior. Our bioinspired ligands have included growth factor sequestering ligands, proteoglycan sequestering ligands, and receptor-binding ligands. Our results demonstrate that bioinspired ligands can control diverse stem cell behaviors, including adhesion, proliferation, migration, phenotypic transformation, and lineage-specific differentiation.

Figure 1: Hydrogel spots bound and arrayed on a swelling hydrogel substrate.

Figure 2: human iPSCs co-cultured with MSCs in synthethic ECM form capillary networks (green: CD31, red: alpha-SMA, blue: DAPI)