Abstract
Pluripotent stem cells, having long been considered the fountain of youth, have caught the attention of many researchers from diverse backgrounds due to their capacity for unlimited self-renewal and potential to differentiate into all cell types. Over the past 15 years, the advanced development of induced pluripotent stem cells (iPSCs) has displayed an unparalleled potential for regenerative medicine, cell-based therapies, modeling human diseases in culture, and drug discovery. The transcription factor quartet (Oct4, Sox2, Klf4, and c-Myc) reprograms highly differentiated somatic cells back to a pluripotent state recapitulated embryonic stem cells (ESCs) in different aspects, including gene expression profile, epigenetic signature, and functional pluripotency. With the prior fruitful studies in SCNT and cell fusion experiments, iPSC finds its place and implicates that the differentiated somatic epigenome retains plasticity for re-gaining the pluripotency and further stretchability to reach a totipotency-like state. These achievements have revolutionized the concept and created a new avenue in biomedical sciences for clinical applications. With the advent of 15 years’ progress-making after iPSC discovery, this review is focused on how the current concept is established by revisiting those essential landmark studies and summarizing its current biomedical applications status to facilitate the new era entry of regenerative therapy.
Highlights
The discovery of induced pluripotent stem cells, a monumental breakthrough, rewrote the conceptual foundation in biology
An observation of the dramatic cell fate change was not made until performing somatic cell nuclear transplant (SCNT) [6,7,8] and heterokaryon experiments [12,13], where a highly differentiated nucleus was reprogrammed to a pluripotent state
Expanded pluripotent stem cells (collectively known as EPS cells (EPSCs)), which allowed for their stable long-term maintenance and conferred a totipotency-like competency in mESC, hESC, and the human fibroblast-derived induced pluripotent stem cells (iPSCs) [133,134]
Summary
The discovery of induced pluripotent stem cells, a monumental breakthrough, rewrote the conceptual foundation in biology. Along with the advances of stem cell biology, the unraveling of pluripotent network formation and the cloning of the Macaque monkey counted as a recent breakthrough in the nuclear reprogramming new culture approaches (e.g., 2i medium and feeder-free) accelerated iPSC development and further allowed for capturing field. Along with the advances of stem cell biology, the unraveling of pluripotent network formation and maintaining EPS cells (expanded potential stem cells) in vitro. Another crucial breakthrough was the production of and new culture approaches (e.g., 2i feeder-free) accelerated the hiPSC-derived. Other crucial breakthrough was the production of the hiPSC-derived RA-responsive FGC formation All of these advances contributed to the first clinical trials of hiPSC-derived retinal cell transplants
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