Clinical Translation of Pluripotent Stem Cell Therapies: Challenges and Considerations

Abstract

Although the clinical outcomes of cell therapy trials have not met initial expectations, emerging evidence suggests that injury-mediated tissue damage might benefit from the delivery of cells or their secreted products. Pluripotent stem cells (PSCs) are promising cell sources primarily because of their capacity to generate stage-and lineage-specific differentiated derivatives. However, they carry inherent challenges for safe and efficacious clinical translation. This Review describes completed or ongoing trials of PSCs, discusses their potential mechanisms of action, and considers how to address the challenges required for them to become a major therapy, using heart repair as a case study.

Cell Therapy With Human ESC-Derived Cardiac Cells: Clinical Perspectives

“…Extracellular vesicles can then shift recipient cell signaling pathways toward cardiac repair through multiple mechanisms, primarily mitigation of apoptosis, inflammation and fibrosis and stimulation of angiogenesis (Garikipati et al, 2018;Zhao et al, 2019), while the re-induction of a mitotic cycle of native cardiomyocytes leading to an increased contractile cell pool remains more controversial. Third, the extracellular vesicle-enriched secretome of stem cellderived cardiac cells (or of MSC) recapitulates (and even sometimes outweighs) the beneficial effects of their parental cells an observation which has now been made across a wide variety of preclinical cardiac (Kervadec et al, 2016;Adamiak et al, 2018;El Harane et al, 2018;Rogers et al, 2019) and non-cardiac disease models (reviewed in Desgres and Menasché, 2019) and is consistent with the finding of an overlap of the microRNA profiles between iPSC-cardiomyocytes (Santoso et al, 2020) or MSC (Shao et al, 2017) and their respective exosomes.…”

Cardiopoietic stem cell therapy restores infarction-altered cardiac proteome

“…Indeed, a recent proteomic study unmasked that adult bone marrow MSCs express, compared to adipose-derived MSCs, a greater yield of angiogenic proteins that translates into a more potent pro-angiogenic phenotype 41 . Furthermore, with increased understanding of the role of secretome components in mediating cell paracrine actions [52][53][54][55][56] , the present study delineated proteome change within the treated heart without defining the extent of contributions arising from the cell itself versus the secretome. Although various -omics approaches offer a means of addressing underlying modes of action, systems interpretation ultimately relies on probabilistic predictive tools.…”

A Manually Curated Database on Clinical Studies Involving Cell Products Derived from Human Pluripotent Stem Cells

“…Since the translation of hPSC research to the clinic started in 2010, we and others have begun to systematically analyze and document the respective clinical studies to assess the progress in this field and provide an overview on planned, completed, and ongoing hPSC-based clinical trials (Desgres and Menasche, 2019;Guhr et al, 2018). Here we present the up-to-date status on the extent, subject, and localization of hPSC-based clinical studies currently under way and provide an easily accessible reference database on hPSC-based clinical studies.…”