Clinical-scale purification of pluripotent stem cell derivatives for cell-based therapies

Abstract

Human pluripotent stem cells (hPSCs) have the potential to revolutionize cell-replacement therapies because of their ability to self renew and differentiate into nearly every cell type in the body. However, safety concerns have delayed the clinical translation of this technology. One cause for this is the capacity that hPSCs have to generate tumors after transplantation. Because of the challenges associated with achieving complete differentiation into clinically relevant cell types, the development of safe and efficient strategies for purifying committed cells is essential for advancing hPSC-based therapies. Several purification strategies have now succeeded in generating non-tumorigenic and homogeneous cell-populations. These techniques typically enrich for cells by either depleting early committed populations from teratoma-initiating hPSCs or by positively selecting cells after differentiation. Here we review the working principles behind separation methods that have facilitated the safe and controlled application of hPSC-derived cells in laboratory settings and pre-clinical research. We underscore the need for improving and integrating purification strategies within differentiation protocols in order to unlock the therapeutic potential of hPSCs.

Keywords: Cell sorting; Human pluripotent stem cells (hPSCs); Target-cell purification; hPSC depletion; hPSC-derived cells.