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. "

    Frontiers in Cell and Developmental Biology 02/2014; 2(2). DOI:10.3389/fcell.2014.00002
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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.
    Chemistry & biology 11/2013; 20(11):1311-1322. DOI:10.1016/j.chembiol.2013.09.016 · 6.65 Impact Factor
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    • "Neurons derived from iPSCs carry the genetic information from patients with a specific mutation or a neurological disease [3, 11, 12]. Over the past few years, the progress in cell reprogramming has accelerated the generation of iPSCs, and iPSCs have now been derived from several easily accessible human cell types, including blood cells, keratinocytes, and dermal fibroblasts [4, 5, 13–15]. The iPSC technology has opened new windows for modeling human diseases, identifying therapeutic targets, developing drug screening systems, and providing continuous autologous cell sources with potential for cell therapies [1, 5, 11, 15–20]. "
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    ABSTRACT: Remarkable advances in cellular reprogramming have made it possible to generate pluripotent stem cells from somatic cells, such as fibroblasts obtained from human skin biopsies. As a result, human diseases can now be investigated in relevant cell populations derived from induced pluripotent stem cells (iPSCs) of patients. The rapid growth of iPSC technology has turned these cells into multipurpose basic and clinical research tools. In this paper, we highlight the roles of iPSC technology that are helping us to understand and potentially treat neurological diseases. Recent studies using iPSCs to model various neurogenetic disorders are summarized, and we discuss the therapeutic implications of iPSCs, including drug screening and cell therapy for neurogenetic disorders. Although iPSCs have been used in animal models with promising results to treat neurogenetic disorders, there are still many issues associated with reprogramming that must be addressed before iPSC technology can be fully exploited with translation to the clinic.
    Neural Plasticity 07/2012; 2012(3):346053. DOI:10.1155/2012/346053 · 3.58 Impact Factor
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