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

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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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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    ABSTRACT: Using human pluripotent stem cells as a source to generate differentiated progenies for regenerative medicine applications has attracted substantial interest during recent years. Having the capability to produce large quantities of human cells that can replace damaged tissue due to disease or injury opens novel avenues for relieving symptoms and also potentially offers cures for many severe human diseases. Although tremendous advancements have been made, there is still much research and development left before human pluripotent stem cell derived products can be made available for cell therapy applications. In order to speed up the development processes, we argue strongly in favor of cross-disciplinary collaborative efforts which have many advantages, especially in a relatively new field such as regenerative medicine based on human pluripotent stem cells. In this review, we aim to illustrate how some of the hurdles for bringing human pluripotent stem cell derivatives from bench-to-bed can be effectively addressed through the establishment of collaborative programs involving academic institutions, biotech industries, and pharmaceutical companies. By taking advantage of the strengths from each organization, innovation and productivity can be maximized from a resource perspective and thus, the chances of successfully bringing novel regenerative medicine treatment options to patients increase.
    Clinical and Translational Medicine 05/2014; 3:9. DOI:10.1186/2001-1326-3-9
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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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    ABSTRACT: One aim of stem cell-based therapy is to utilize pluripotent stem cells (PSCs) as a supplementary source of cells to repair or replace tissues or organs that have ceased to function due to severe tissue damage. However, PSC-based therapy requires extensive research to ascertain if PSC derivatives are functional without the risk of tumorigenicity, and also do not engender severe immune rejection that threatens graft survival and function. Recently, the suitability of induced pluripotent stem cells applied for patient-tailored cell therapy has been questioned since the discovery of several genetic and epigenetic aberrations during the reprogramming process. Hence, it is crucial to understand the effect of these abnormalities on the immunogenicity and survival of PSC grafts. As induced PSC-based therapy represents a hallmark for the potential solution to prevent and arrest immune rejection, this review also summarizes several up-to-date key findings in the field.
    Current Stem Cell Research & Therapy 10/2013; 9(1). DOI:10.2174/1574888X113086660068 · 2.21 Impact Factor
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    ABSTRACT: The unexpected discovery that somatic cells can be reprogrammed to a pluripotent state yielding induced pluripotent stem cells has made it possible to produce cardiovascular cells exhibiting inherited traits and disorders. Use of these cells in high throughput analyses should broaden our insight into fundamental disease mechanisms and provide many benefits for patients, including new therapeutics and individually tailored therapies. Here we review recent progress in generating induced pluripotent stem cell-based models of cardiovascular disease and their multiple applications in drug development.
    Circulation Research 02/2013; 112(3):534-548. DOI:10.1161/CIRCRESAHA.111.250266 · 11.02 Impact Factor
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