Abstract
The discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka in 2006 was heralded as a major breakthrough of the decade in stem cell research. The ability to reprogram human somatic cells to a pluripotent embryonic stem cell-like state through the ectopic expression of a combination of embryonic transcription factors was greeted with great excitement by scientists and bioethicists. The reprogramming technology offers the opportunity to generate patient-specific stem cells for modeling human diseases, drug development and screening, and individualized regenerative cell therapy. However, fundamental questions have been raised regarding the molecular mechanism of iPSCs generation, a process still poorly understood by scientists. The efficiency of reprogramming of iPSCs remains low due to the effect of various barriers to reprogramming. There is also the risk of chromosomal instability and oncogenic transformation associated with the use of viral vectors, such as retrovirus and lentivirus, which deliver the reprogramming transcription factors by integration in the host cell genome. These challenges can hinder the therapeutic prospects and promise of iPSCs and their clinical applications. Consequently, extensive studies have been done to elucidate the molecular mechanism of reprogramming and novel strategies have been identified which help to improve the efficiency of reprogramming methods and overcome the safety concerns linked with iPSC generation. Distinct barriers and enhancers of reprogramming have been elucidated, and non-integrating reprogramming methods have been reported. Here, we summarize the progress and the recent advances that have been made over the last 10 years in the iPSC field, with emphasis on the molecular mechanism of reprogramming, strategies to improve the efficiency of reprogramming, characteristics and limitations of iPSCs, and the progress made in the applications of iPSCs in the field of disease modelling, drug discovery and regenerative medicine. Additionally, this study appraises the role of genomic editing technology in the generation of healthy iPSCs.
Highlights
The development of induced pluripotent stem cells in 2006 by Shinya Yamanaka was a remarkable breakthrough that was made possible by many research findings by past and current scientists in related fields
In 1962, Sir John Gurdon achieved the first example of cellular reprogramming by reporting the generation of tadpoles from enucleated unfertilized frog egg cells that had been transplanted with the nucleus from intestinal epithelial somatic cells of tadpoles (Gurdon, 1962)
We provide an overview of the progress made in induced pluripotent stem cells (iPSCs) technology in the last decade
Summary
The development of induced pluripotent stem cells (iPSCs) in 2006 by Shinya Yamanaka was a remarkable breakthrough that was made possible by many research findings by past and current scientists in related fields. A year later in 2007, Yamanaka and his team applied the same reprogramming method for adult human fibroblast to generate human iPSCs (hiPSCs) and James Thomson’s group reported the generation of the same hiPSCs though using a different delivery system, the lentivirus and a different set of four factors: Oct 3/4, Sox, Nanog, and Lin 28 (Takahashi et al, 2007; Yu et al, 2007). For their remarkable revolutionary discoveries, Shinya Yamanaka and John B. We will briefly discuss the potential application of iPSCs in the field of disease modeling, drug development, and regenerative medicine
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