Immunogenicity of Pluripotent Stem Cells and Their Derivatives

Stanford University School of Medicine, Lorry Lokey Stem Cell Research Bldg, 265 Campus Dr, Room G1120B, Stanford, CA 94305-5454. .
Circulation Research (Impact Factor: 11.02). 02/2013; 112(3):549-561. DOI: 10.1161/CIRCRESAHA.111.249243
Source: PubMed


The ability of pluripotent stem cells to self-renew and differentiate into all somatic cell types brings great prospects to regenerative medicine and human health. However, before clinical applications, much translational research is necessary to ensure that their therapeutic progenies are functional and nontumorigenic, that they are stable and do not dedifferentiate, and that they do not elicit immune responses that could threaten their survival in vivo. For this, an in-depth understanding of their biology, genetic, and epigenetic make-up and of their antigenic repertoire is critical for predicting their immunogenicity and for developing strategies needed to assure successful long-term engraftment. Recently, the expectation that reprogrammed somatic cells would provide an autologous cell therapy for personalized medicine has been questioned. Induced pluripotent stem cells display several genetic and epigenetic abnormalities that could promote tumorigenicity and immunogenicity in vivo. Understanding the persistence and effects of these abnormalities in induced pluripotent stem cell derivatives is critical to allow clinicians to predict graft fate after transplantation, and to take requisite measures to prevent immune rejection. With clinical trials of pluripotent stem cell therapy on the horizon, the importance of understanding immunologic barriers and devising safe, effective strategies to bypass them is further underscored. This approach to overcome immunologic barriers to stem cell therapy can take advantage of the validated knowledge acquired from decades of hematopoietic stem cell transplantation.

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Available from: Joseph C Wu, Mar 23, 2015
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    • "Alternatives include a systemic approach via intravenous infusions. Besides encapsulation, other options to avoid a devastating immune reaction would be to generate banks of matching cell lines (so-called “haplobanks”) or to engineer the genome of cells to cause less response from the host by for example knocking out immune-reaction causing antigens [21]. The use of mesenchymal stromal cells as immunomodulatory agents also represents an alternative to suppress immune reactions caused by implanted stem cell derivatives [22,23]. "
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    • "In addition to differentiation, increased immunogenicity of undifferentiated ESCs after IFNγ treatment was reported by several studies, all of which concurred to similar results that no teratomas or only quickly regressing teratomas were formed [19-21] (Fig. 1). These findings suggest the possibility of PSC-derived graft failure, if transplanted into an unfavorable environment that promotes the upregulation of MHC molecules [22]. "
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