Induced pluripotent stem cells (iPSCs) are a new type of stem cell that is generated by reprogramming the genome of an adult somatic cell, such as a skin fibroblast, to a pluripotent state. Such iPSCs share many similarities with embryonic stem cells (ESCs). Reprogramming of adult somatic cells to iPSCs requires certain pluripotency factors, including the transcription factors Oct4, Sox2, and Klf4. These iPSCs are able to renew themselves indefinitely and to differentiate into many different cell types, including pancreatic-β cells, liver hepatocytes, cardiomyocytes, hematopoietic cells, and dopaminergic neurons. Consequently, there has been much enthusiasm about using iPSCs to generate tissues to treat a variety of diseases, including diabetes, liver cirrhosis, leukemia, and Parkinson’s disease, but ultimately how useful these cells will be for regenerative medicine is still not clear.
Fig. Roadblocks to translating human iPSC technology to the clinic.
Human iPSC technology potentially can be used for screening new cancer drugs (blue box) and ultimately for providing cells for transplant to treat a variety of diseases, including cancer (yellow box). Genetic mutations can be corrected in patient-derived iPSCs by gene targeting approaches. The main hurdles to using patient-specific iPSCs for disease modeling, drug screening, and transplantation purposes are (i) a lack of effective differentiation protocols, (ii) little or no engraftment capability for the majority of human iPSC-derived specialized cells, (iii) difficulties in modeling multifactorial diseases, (iv) the need for GMP-compliant conditions at each step, and (v) safety concerns regarding the potential tumorigenicity of iPSCs associated with their pluripotent state or with insertional- or culture-driven mutagenesis. Dotted arrow, not yet tested; solid arrow, only a few studies available; blue arrow, feasible but requires further study.
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