The advancement of human pluripotent stem cell-derived therapies into the clinic

Abstract

Human pluripotent stem cells (hPSCs) offer many potential applications for drug screening and 'disease in a dish' assay capabilities. However, a more ambitious goal is to develop cell therapeutics using hPSCs to generate and replace somatic cells that are lost as a result of disease or injury. This Spotlight article will describe the state of progress of some of the hPSC-derived therapeutics that offer the most promise for clinical use. Lessons from developmental biology have been instrumental in identifying signaling molecules that can guide these differentiation processes in vitro, and will be described in the context of these cell therapy programs.

Function Follows Form ― A Review of Cardiac Cell Therapy ―

“…Recruitment for this multinational, open-label and random-Despite the promise of hPSC-CM transplantation, significant challenges to clinical translation remain, including scaling cell manufacturing to clinical levels, graft tolerance and immunosuppression, tumorigenicity, delivery, and most acutely, arrhythmogenesis. 19,89 In earlier work with mice, rats and guinea pigs, no arrhythmias were observed after hESC-CM transplantation. When we moved into macaques, however, we observed a significant burden of ventricular arrhythmias.…”

“…The most promising preclinical investigations of cardiac remuscularization therapy returns to the premise that meaningful and durable recovery of injured myocardium requires genuine and direct regeneration of lost myocardium to restore contractility. 89,128,132 The extensive experience with adult cell therapy, however, provides a reassuring framework of infrastructure for the safe delivery of cells in such trials, as well as a cautionary lesson in better understanding of underlying biology and establishing protocols through careful preclinical investigation and validation. The non-contractile benefit observed with adult cells warrants further basic research to identify the mechanism of action.…”

Identification and characterization of splenic adherent cells forming densely‐packed colonies

“…Therefore, ESCs provide an excellent paradigm for studying mammalian early embryogenesis. Because of this remarkable property, ESCs and induced pluripotent cells (iPSCs), another pluripotent cell type, hold great promise for regenerative medicine, especially because the establishment of iPSCs eliminates two major hurdles, in other words, immune‐rejection and ethnic issues, which make ESCs difficult for clinical use (Bock et al., ; Mallon et al., ; Soldner et al., ; Thies & Murry, ; Trounson & DeWitt, ). However, the production of iPSCs requires extensive genetic modification and/or chemical treatment with somatic cells, which may cause unpredicted abnormalities.…”

Development of an Alginate Array Platform to Decouple the Effect of Multiparametric Perturbations on Human Pluripotent Stem Cells During Pancreatic Differentiation

“…Human pluripotent stem cells (hPSCs) have enormous potential in tissue engineering and cell therapy applications . These cells have two distinct characteristics which make them highly attractive: they can become any cell type in the body, and can self‐renew indefinitely.…”

“…Human pluripotent stem cells (hPSCs) have enormous potential in tissue engineering and cell therapy applications. [1] These cells have two distinct characteristics which make them highly attractive: they can become any cell type in the body, and can self-renew indefinitely. Over the last two decades there has been concentrated effort to derive functional organ specific cells from hPSCs, which include, but are not limited to, cardiac cells, [2][3][4] neurons, [5,6] hepatocytes, [7][8][9] and pancreatic beta cells.…”