Extracellular Matrices Derived from Pluripotent Stem Cell Aggregates for Tissue Development

Pluripotent stem cells (PSCs) secrete large amounts of endogenous extracellular matrices (ECMs), which play an important role in regulating PSC self-renewal, lineage commitment, and tissue morphogenesis.  ECMs derived from PSCs have broader signaling capacity compared to somatic ECMs and contain the unique signaling networks that regulate the self-renewal and lineage specification during tissue development.  In this study, ECMs from undifferentiated PSC aggregates or differentiated embryoid bodies at different developmental stages and lineage specifications were decellularized and their capacities to direct PSC proliferation and differentiation were characterized.  The results demonstrate that the PSC-derived ECMs were able to influence PSC proliferation and differentiation by direct interactions with the cells and by influencing the signaling functions of the regulatory macromolecules.  Proteomic analysis (by LC-MS) indicated the shared and distinct proteins in ECMs derived from undifferentiated and different types of differentiated aggregates.  To enhance the stability of PSC-derived ECMs, ECMs were crosslinked by a natural cross-linker which increased the stiffness of ECMs.  The effect of biomechanical properties of ECMs on neural differentiation was also evaluated.  Taken together, the PSC-derived ECMs have the potential to direct lineage- and development-specific cellular responses for in vitro applications or in vivo cell delivery.