Defining cell-matrix combination products in the era of pluripotency

Human pluripotent stem (hPS) cells provide an attractive opportunity for the manufacture of a wide array of therapeutic cell types. The challenges to commercialization include the thousand-fold diversity of cell types emerging from hPS cells and the associated difficulties in validating processes to reliably generate cells with precise identity and purity. Improved methods of controlling the dosage and migration of hPS-derived cells in solid tissues are also needed. To directly address these issues, we clonally expanded proliferating lineages of cells that were intermediate in regard to their state of differentiation between hPS and terminally differentiated cells. These cells called monoclonal embryonic progenitors (hEP), are expandable mortal lineages with diverse site-specific homeobox gene expression and multipotentiality. In this review, we discuss methods of generating combination products wherein the fate space of precisely identified monoclonal hEP cells is mapped by differentiating the cells in vitro in HyStem-3D bead arrays in the presence of diverse growth factors. This combination of discovery processes has the potential to translate directly into cell-matrix formulations that can be used to generate pre-clinical data leading to human clinical trials and potentially new medical therapies.