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    ABSTRACT: Pluripotent stem cells (PSCs) including induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) have emerged as a promising source for treating incurable diseases. Problems that urgently need to be resolved before the clinical application include avoiding potential xenopathogenic transmission and immune rejection that may be caused by the exposure of PSCs to animal-derived products. In addition, an efficient feeder cell-free culture condition would be required for reducing batch-to-batch variation and facilitating scale-up. Therefore, establishing an efficient xeno-free and extracelluar matrix-based culture system is a prerequisite for the clinical application of PSCs. In this study, by blocking protein kinase C and histone deacetylase activities, we formulated a medium that, in combination with vitronectin as an extracellular matrix, not only allows the long-term culture of hESCs and iPSCs but also efficiently generates xeno-free iPSCs. This xeno-free and feeder cell-free culture system would facilitate the clinical applications of both iPSC- and ESC-based cell therapies in the future.
    Biomaterials 11/2012; · 8.31 Impact Factor
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    ABSTRACT: The potential to develop into any cell type makes human pluripotent stem cells (hPSCs) one of the most promising sources for regenerative treatments. Hurdles to their clinical applications include (1) formation of heterogeneously differentiated cultures, (2) the risk of teratoma formation from residual undifferentiated cells, and (3) immune rejection of engrafted cells. The recent production of human isogenic (genetically identical) induced PSCs (hiPSCs) has been proposed as a "solution" to the histocompatibility barrier. In theory, differentiated cells derived from patient-specific hiPSC lines should be histocompatible to their donor/recipient. However, propagation, maintenance, and non-physiologic differentiation of hPSCs in vitro may produce other, likely less powerful, immune responses. In light of recent progress towards the clinical application of hPSCs, this review focuses on two antigen presentation phenomena that may lead to rejection of isogenic hPSC derivates: namely, the expression of aberrant antigens as a result of long-term in vitro maintenance conditions or incomplete somatic cell reprogramming, and the unbalanced presentation of receptors and ligands involved in immune recognition due to accelerated differentiation. Finally, we discuss immunosuppressive approaches that could potentially address these immunological concerns.
    Methods in molecular biology (Clifton, N.J.) 01/2013; 1029:17-31. · 1.29 Impact Factor
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    ABSTRACT: The first derivation of human embryonic stem cells brought with it a clear understanding that animal models of human disease might be replaced by an unlimited supply of human cells for research, drug discovery, and drug development. With the advent of clinical trials using human pluripotent stem cell-based therapies, it is both timely and relevant to reflect on factors that will facilitate future translation of this technology. Human pluripotent cells are increasingly being used to investigate the molecular mechanisms that underpin normal and pathological human development. Their differentiated progeny are also being used to identify novel pharmaceuticals, to screen for toxic effects of known chemicals, and to investigate cell or tissue transplantation strategies. The intrinsic assumption of these research efforts is that the information gained from these studies will be more accurate, and therefore of greater relevance, than traditional investigations based on animal models of human disease and injury. This review will therefore evaluate how animals and animal-derived products are used for human pluripotent stem cell research, and will indicate how efforts to further reduce or remove animals and animal products from this research will increase the clinical translation of human pluripotent stem cell technologies through drug discovery, toxicology screening, and cell replacement therapies.
    Stem Cell Research & Therapy 03/2013; 4(2):21. · 4.63 Impact Factor

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