The Potential for Immunogenicity of Autologous Induced Pluripotent Stem Cell-derived Therapies

Scheiner, Zachary S.; Talib, Sohel; Feigal, Ellen G.

doi:10.1074/jbc.r113.509588

Cited by 52 publications

(33 citation statements)

References 66 publications

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“…Non‐HLA genetic and nongenetic determinants are known to confer risk of rejection [15, 18]. Autologous derived stems cells, for example, particularly iPSCs, can also be immunogenic or can stimulate autoimmune reactions [20, 21]. Depending on the circumstance, such as in urgent situations, alternative donors and various levels of compatibility may be warranted [22].…”

Section: Discussionmentioning

confidence: 99%

Proceedings: Human Leukocyte Antigen Haplo-Homozygous Induced Pluripotent Stem Cell Haplobank Modeled After the California Population: Evaluating Matching in a Multiethnic and Admixed Population

Pappas¹,

Gourraud

Gall³

et al. 2015

Stem Cells Translational Medicine

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The development of a California-based induced pluripotent stem cell (iPSC) bank based on human leukocyte antigen (HLA) haplotype matching represents a significant challenge and a valuable opportunity for the advancement of regenerative medicine. However, previously published models of iPSC banks have neither addressed the admixed nature of populations like that of California nor evaluated the benefit to the population as a whole. We developed a new model for evaluating an iPSC haplobank based on demographic and immunogenetic characteristics reflecting California. The model evaluates haplolines or cell lines from donors homozygous for a single HLA-A, HLA-B, HLA-DRB1 haplotype. We generated estimates of the percentage of the population matched under various combinations of haplolines derived from six ancestries (black/African American, American Indian, Asian/Pacific Islander, Hispanic, and white/not Hispanic) and data available from the U.S. Census Bureau, the California Institute for Regenerative Medicine, and the National Marrow Donor Program. The model included both cis (haplotype-level) and trans (genotype-level) matching between a modeled iPSC haplobank and the recipient population following resampling simulations. We showed that serving a majority (>50%) of a simulated California population through cis matching would require the creation, redundant storage, and maintenance of almost 207 different haplolines representing the top 60 most frequent haplotypes from each ancestry group. Allowances for trans matching reduced the haplobank to fewer than 141 haplolines found among the top 40 most frequent haplotypes. Finally, we showed that a model optimized, custom haplobank was able to serve a majority of the California population with fewer than 80 haplolines.

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Section: Discussionmentioning

confidence: 99%

Proceedings: Human Leukocyte Antigen Haplo-Homozygous Induced Pluripotent Stem Cell Haplobank Modeled After the California Population: Evaluating Matching in a Multiethnic and Admixed Population

Pappas¹,

Gourraud

Gall³

et al. 2015

Stem Cells Translational Medicine

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“…34 However, in some studies, syngeneic ESC and iPSC – the latter even after in-vitro differentiation – have been found to generate an immune response (mediated by T cells and macrophages) when transplanted leading to their rejection. 35,36 Unlike ESC and iPSC-derived cells, which may potentially be immunogenic, ICC-SC are in fact immunosuppressive and thus may be better suited to treat disorders mediated by injury or loss of ICC.…”

Section: Discussionmentioning

confidence: 99%

Stem Cells for Murine Interstitial Cells of Cajal Suppress Cellular Immunity and Colitis Via Prostaglandin E2 Secretion

et al. 2015

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Background & Aims Following allogeneic transplantation, murine stem cells (SC) for interstitial cells of Cajal (ICC), electrical pacemaker and neuromodulator cells of the gut, incorporated into gastric ICC networks indicating in-vivo immunosuppression. Immunosuppression is characteristic of bone marrow- and other non-gut-derived mesenchymal stem cells (MSC), which are emerging as potential therapeutic agents against autoimmune diseases including inflammatory bowel disease. Therefore, we investigated whether gut-derived ICC-SC could also mitigate experimental colitis and studied the mechanisms of ICC-SC-mediated immunosuppression in relation to MSC-induced pathways. Methods Isolated ICC-SC were studied by transcriptome profiling, cytokine assays, flow cytometry, mixed lymphocyte reaction and T cell proliferation assay. Mice with acute and chronic colitis induced by dextran sulfate sodium and T cell transfer, respectively, were administered ICC-SC intraperitoneally and evaluated for disease activity by clinical and pathological assessment and for ICC-SC homing by live imaging. Results Unlike strain-matched dermal fibroblasts, intraperitoneally administered ICC-SC preferentially homed to the colon and reduced the severity of both acute and chronic colitis assessed by clinical and blind pathological scoring. ICC-SC profoundly suppressed T cell proliferation in vitro. Similarly to MSC, ICC-SC strongly expressed cyclooxygenase 1/2 and basally secreted prostaglandin E2. Indomethacin, a cyclooxygenase inhibitor, countered the ICC-SC-mediated suppression of T cell proliferation. In contrast, we found no role for regulatory T cell-, programmed death receptor- and transforming growth factor-β-mediated mechanisms reported in MSC; and transcriptome profiling did not support a relationship between ICC-SC and MSC. Conclusion Murine ICC-SC belong to a class different from MSC and potently mitigate experimental colitis via prostaglandin E2-mediated immunosuppression.

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“…It will also be important to monitor changes in the expression pattern and level of the genes due to aberrant DNA methylation during reprograming process which could potentially evoke an immune responses in transplant recipients even when autologously derived (Zhao et al, 2011; Araki et al, 2013; Guha et al, 2013). If this is unavoidable, minor immunogenicity may be addressed using conventional immunosuppressives or short term monoclonal antibody-mediated co-stimulation/adhesion blockade of host T cells (Scheiner et al, 2014). As the technology develops, these risk and benefits, as well as new challenges, are likely to come to the forefront.…”

Section: Challenges and Recent Progress For Ipsc Derived Cellsmentioning

confidence: 99%

Induced Pluripotent Stem Cells for Traumatic Spinal Cord Injury

Khazaei

Ahuja

Fehlings

2017

Front. Cell Dev. Biol.

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Spinal cord injury (SCI) is a common cause of mortality and neurological morbidity. Although progress had been made in the last decades in medical, surgical, and rehabilitation treatments for SCI, the outcomes of these approaches are not yet ideal. The use of cell transplantation as a therapeutic strategy for the treatment of SCI is very promising. Cell therapies for the treatment of SCI are limited by several translational road blocks, including ethical concerns in relation to cell sources. The use of iPSCs is particularly attractive, given that they provide an autologous cell source and avoid the ethical and moral considerations of other stem cell sources. In addition, different cell types, that are applicable to SCI, can be created from iPSCs. Common cell sources used for reprogramming are skin fibroblasts, keratinocytes, melanocytes, CD34+ cells, cord blood cells and adipose stem cells. Different cell types have different genetic and epigenetic considerations that affect their reprogramming efficiencies. Furthermore, in SCI the iPSCs can be differentiated to neural precursor cells, neural crest cells, neurons, oligodendrocytes, astrocytes, and even mesenchymal stromal cells. These can produce functional recovery by replacing lost cells and/or modulating the lesion microenvironment.

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The Potential for Immunogenicity of Autologous Induced Pluripotent Stem Cell-derived Therapies

Cited by 52 publications

References 66 publications

Proceedings: Human Leukocyte Antigen Haplo-Homozygous Induced Pluripotent Stem Cell Haplobank Modeled After the California Population: Evaluating Matching in a Multiethnic and Admixed Population

Proceedings: Human Leukocyte Antigen Haplo-Homozygous Induced Pluripotent Stem Cell Haplobank Modeled After the California Population: Evaluating Matching in a Multiethnic and Admixed Population

Stem Cells for Murine Interstitial Cells of Cajal Suppress Cellular Immunity and Colitis Via Prostaglandin E2 Secretion

Induced Pluripotent Stem Cells for Traumatic Spinal Cord Injury

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