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Immunogenicity of In Vitro Maintained and Matured Populations: Potential Barriers to Engraftment of Human Pluripotent Stem Cell Derivatives

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Embryonic Stem Cell Immunobiology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1029))

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.

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Authors and Affiliations

  1. Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA

    Chad Tang, Irving L. Weissman & Micha Drukker

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  1. Chad Tang
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  2. Irving L. Weissman
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  1. Dept. Internal Medicine, Div. Allergy & Immunology, University of Iowa, Hawkins Drive 200, Iowa City, 52242, Iowa, USA

    Nicholas Zavazava

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Tang, C., Weissman, I.L., Drukker, M. (2013). Immunogenicity of In Vitro Maintained and Matured Populations: Potential Barriers to Engraftment of Human Pluripotent Stem Cell Derivatives. In: Zavazava, N. (eds) Embryonic Stem Cell Immunobiology. Methods in Molecular Biology, vol 1029. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-478-4_2

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  • DOI: https://doi.org/10.1007/978-1-62703-478-4_2

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