Inducing iPSCs to Escape the dish

Department of Cell Biology and Human Anatomy, University of California Davis School of Medicine, Sacramento, CA 95817, USA.
Cell stem cell (Impact Factor: 22.27). 08/2011; 9(2):103-11. DOI: 10.1016/j.stem.2011.07.006
Source: PubMed


Induced pluripotent stem cells (iPSCs) hold great promise for autologous cell therapies, but significant roadblocks remain to translating iPSCs to the bedside. For example, concerns about the presumed autologous transplantation potential of iPSCs have been raised by a recent paper demonstrating that iPSC-derived teratomas were rejected by syngeneic hosts. Additionally, the reprogramming process can alter genomic and epigenomic states, so a key goal at this point is to determine the clinical relevance of these changes and minimize those that prove to be deleterious. Finally, thus far few studies have examined the efficacy and tumorigenicity of iPSCs in clinically relevant transplantation scenarios, an essential requirement for the FDA. We discuss potential solutions to these hurdles to provide a roadmap for iPSCs to "jump the dish" and become useful therapies.

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Available from: Bonnie L Barrilleaux
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    • "In 2012, Yamanaka and Gurdon were awarded the Nobel Prize for Physiology or Medicine for the discovery of generation of iPSCs and nuclear reprogramming; in both of which, mature somatic cells can be converted to pluripotent stem cells (Gurdon, 1962; Takahashi and Yamanaka, 2006; Yamanaka and Blau, 2010). However, there are several safety concerns such as the potential risk of tumorigenesis and the genetic and epigenetic aberrations after transplantation of iPSC-derived cells, partly diminishing the enthusiasm of using iPSC technology for mediated regenerative medicine in humans (Barrilleaux and Knoepfler, 2011). Direct reprogramming can overcome these difficulties since somatic cells can be directly reprogrammed into particular cell types without going through the iPSC or pluripotent stage. "

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    • "The current iPS cell-engineering process may produce cells of variable quality (Gore et al., 2011; Kim et al., 2010). Similarly to any other product , cost and the time consumed are also significant concerns for the generation and marketing of clinical grade iPS cells (CGiPS) (Barrilleaux and Knoepfler, 2011). It may take months to validate and differentiate iPS cells prior to their clinical use. "
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    ABSTRACT: Adult mammals possess limited ability to regenerate their lost tissues or organs. The epoch-making strategy of inducing pluripotency in somatic cells incorporates multiple applications in regenerative medicine. However, concerns about the clinical translation of induced pluripotent stem (iPS) cells still exist because of the occurrence of aberrancies, even in genome integration-free methods. As cellular reprogramming is multi-gene-oriented, versatile, bioactive small molecules could concomitantly modulate the transcriptional machinery and aid the generation of clinical grade iPS cells. The availability of optimal cell sources has additional influence on the clinical translation of iPS cells. Herein we provide a critical overview of methods and cell sources available for iPS cell production. We think the review will be a useful resource for researchers who aim to develop small molecules for speeding up the journey of iPS cells from the laboratory to the clinic.
    Preview · Article · Nov 2013 · Chemistry & biology
    • "For example, the reprogramming process (especially when performed via retroviral transduction) has the potential to alter both the genomic and epigenomic state of the iPSCs, tending to push them towards tumorigenicity and away from the generation of normally differentiated daughter cells capable of forming functional target tissues. In addition, the immune tolerance of recipients to autologous iPSC transplantation has been questioned (Barrilleaux and Knoepfler, 2011). To avoid repeating the mistakes made with gene therapy, many researchers in the iPSC field have recommended additional basic research, efficiency and safety testing in animal models before moving iPSCs into the clinical arena (Hyun et al., 2008; Wilson, 2009). "
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    ABSTRACT: Induced pluripotent stem cells (iPSCs) can now be derived from a tissue biopsy and represent a promising new platform for disease modelling, drug and toxicity testing, biomarker development and cell-based therapies for regenerative medicine. In regenerative medicine, large animals may represent the best models for man, and thereby provide invaluable systems in which to test the safety and the potential of iPSCs. Hence, testing iPSCs in veterinary species may serve a double function, namely, developing therapeutic products for regenerative medicine in veterinary patients while providing valuable background information for human clinical trials. The production of iPSCs from livestock or wild species is attractive because it could improve efficiency and reduce costs in various fields, such as transgenic animal generation and drug development, preservation of biological diversity, and because it also offers an alternative to xenotransplantation for in vivo generation of organs. Although the technology of cellular reprogramming using the so-called 'Yamanaka factors' is in its peak expectation phase and many concerns still need to be addressed, the rapid technical progress suggests that iPSCs could contribute significantly to novel therapies in veterinary and biomedical practice in the near future. This review provides an overview of the potential applications of iPSCs in veterinary medicine.
    No preview · Article · Oct 2013 · The Veterinary Journal
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