Pluripotent Stem Cells: Immune to the Immune System?

Department of Medicine and Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Science translational medicine (Impact Factor: 15.84). 12/2012; 4(164):164ps25. DOI: 10.1126/scitranslmed.3005090
Source: PubMed


Human embryonic stem cells (hESCs), initially thought to be immune privileged cells, are now known to be susceptible to immune recognition. Human induced pluripotent stem cells (iPSCs) have been proposed as a potential source of autologous stem cells for therapy, but even these autologous stem cells may be targets of immune rejection. With clinical trials on the horizon, it is imperative that the immunogenicity of hESCs and iPSCs be definitively understood.

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    • "However, their utility is limited by immunological rejection upon transplantation of the allogeneic ESCs or differentiated progeny. Rejection has been observed in animal modeling (Pearl et al., 2012; Wu et al., 2008). One alternative is to use autologous induced pluripotent stem cells (iPSCs) (Wu and Hochedlinger, 2011). "
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    ABSTRACT: Embryonic stem cells (ESCs) hold promise for the treatment of many medical conditions; however, their utility is limited by immune rejection. The objective of our study is to establish tolerance or promote engraftment of transplanted ESCs as well as mature cell populations derived from ESCs. Luciferase (luc(+))-expressing ESCs were utilized to monitor the survival of the ESCs and differentiated progeny in living recipients. Allogeneic recipients conditioned with fractioned total lymphoid irradiation (TLI) and anti-thymocyte serum (ATS) or TLI plus regulatory T cells (Treg) promoted engraftment of ESC allografts after transplantation. Following these treatments, the engraftment of transplanted terminally differentiated endothelial cells derived from ESCs was also significantly enhanced. Our findings provide clinically translatable strategies of inducing tolerance to adoptively transferred ESCs for cell replacement therapy of medical disorders. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
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    ABSTRACT: Embryonic stem cell (ESC)-based transplantation is considered a promising novel therapy for a variety of diseases. This is bolstered by the suggested immune-privileged properties of ESCs. In this study, we used in vivo bioluminescent imaging (BLI) to non-invasively track the fate of transplanted murine ESCs (mESCs), which are stably transduced with a double fusion reporter gene consisting of firefly luciferase (FLuc) and enhanced green fluorescent protein (eGFP). Following syngeneic intramuscular transplantation of 1 x 10(6) mESCs, the cells survived and differentiated into teratomas. In contrast, allogeneic mESC transplants were infiltrated by a variety of inflammatory cells, leading to rejection within 28 days. Acceleration of rejection was observed when mESCs were allotransplanted following prior sensitization of the host. Finally, we demonstrate that the mESC derivatives were more rapidly rejected compared to undifferentiated mESCs. These data show that mESCs do not retain immune-privileged properties in vivo and are subject to immunological rejection as assessed by novel molecular imaging approaches.
    Full-text · Article · Jun 2008 · Stem cells and development
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    ABSTRACT: 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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