Abstract
Human pluripotent stem cells (hPSC) are known to acquire chromosomal abnormalities, which range from point mutations to large copy number changes, including full chromosome aneuploidy. These aberrations have a wide-ranging influence on the state of cells, in both the undifferentiated and differentiated state. Currently, very little is known on how these abnormalities will impact the clinical translation of hPSC, and particularly their potential to prime cells for oncogenic transformation. A further complication is that many of these abnormalities exist in a mosaic state in culture, which complicates their detection with conventional karyotyping methods. In this review we discuss current knowledge on how these aberrations influence the cell state and how this may impact the future of research and the cells’ clinical potential.
Highlights
Research Group Reproduction and Genetics, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB), 1090 Jette, Belgium
Our understanding of the biology of Human pluripotent stem cells (hPSC) has progressed significantly, with expansion in the number of cell types available for differentiation resulting in immense progress in the field as a whole
It is clear that these hurdles are not insurmountable and improved understanding of hPSC biology will lead to innovative solutions to the issues presented
Summary
Stem cells are defined by their ability to self-renew and differentiate into more specialized cell types. The potential applications of human pluripotent stem cells (hPSC) are many, but the most important fall into the fields of drug discovery, disease modeling, and regenerative medicine. At their core, each of these applications takes advantage of the differentiated derivatives of hPSC, and the relative ease with which they can be generated. Reprogramming somatic cells offers further advantages through the generation of patient-derived iPSCs, opening up the possibility of “patient-derived disease-in-a-dish models”, whereby cell types with disease-specific phenotypes are readily created These models offer a more realistic source material for drug screening and have led to the discovery and subsequent clinical trials of drugs for progressive supranuclear palsy (Gosuranemab, currently in phase II), amyotrophic lateral sclerosis (retigabine, currently in phase II; bosutinib, currently in phase I; ROPI, phase I/IIa), and spinal muscular atrophy (RG7800, entering phase II) [3,4,5].
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