Defining cell-matrix combination productsin the era of pluripotency

摘要

Human pluripotent stem (hPS) cells provide an attractiveopportunity for the manufacture of a wide array of therapeuticcell types. The challenges to commercialization include thethousand-fold diversity of cell types emerging from hPScells and the associated diffculties in validating processesto reliably generate cells with precise identity and purity.Improved methods of controlling the dosage and migration ofhPS-derived cells in solid tissues are also needed. To directlyaddress these issues, we clonally expanded proliferatinglineages of cells that were intermediate in regard to their stateof differentiation between hPS and terminally differentiatedcells. These cells called monoclonal embryonic progenitors(hEP), are expandable mortal lineages with diverse sitespecifichomeobox gene expression and multipotentiality. Inthis review, we discuss methods of generating combinationproducts wherein the fate space of precisely identifiedmonoclonal hEP cells is mapped by differentiating the cellsin vitro in HyStem-4D bead arrays in the presence of diversegrowth factors. This combination of discovery processes hasthe potential to translate directly into cell-matrix formulationsthat can be used to generate pre-clinical data leading tohuman clinical trials and potentially new medical therapies.