Evaluation of the immunogenicity of human iPS cell-derived neural stem/progenitor cells in vitro
To achieve the goal of a first-in-human trial for human induced pluripotent stem cell (hiPSC)-based transplantation for the treatment of various diseases, allogeneic human leukocyte antigen (HLA)-matched hiPSC cell banks represent a realistic tool from the perspective of quality control and cost per...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-03-01
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| Series: | Stem Cell Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1873506117300077 |
| _version_ | 1818063256934154240 |
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| author | Masahiro Ozaki Akio Iwanami Narihito Nagoshi Jun Kohyama Go Itakura Hiroki Iwai Soraya Nishimura Yuichiro Nishiyama Soya Kawabata Keiko Sugai Tsuyoshi Iida Kohei Matsubayashi Miho Isoda Rei Kashiwagi Yoshiaki Toyama Morio Matsumoto Hideyuki Okano Masaya Nakamura |
| author_facet | Masahiro Ozaki Akio Iwanami Narihito Nagoshi Jun Kohyama Go Itakura Hiroki Iwai Soraya Nishimura Yuichiro Nishiyama Soya Kawabata Keiko Sugai Tsuyoshi Iida Kohei Matsubayashi Miho Isoda Rei Kashiwagi Yoshiaki Toyama Morio Matsumoto Hideyuki Okano Masaya Nakamura |
| author_sort | Masahiro Ozaki |
| collection | DOAJ |
| description | To achieve the goal of a first-in-human trial for human induced pluripotent stem cell (hiPSC)-based transplantation for the treatment of various diseases, allogeneic human leukocyte antigen (HLA)-matched hiPSC cell banks represent a realistic tool from the perspective of quality control and cost performance. Furthermore, considering the limited therapeutic time-window for acute injuries, including neurotraumatic injuries, an iPS cell bank is of potential interest. However, due to the relatively immunoprivileged environment of the central nervous system, it is unclear whether HLA matching is required in hiPSC-derived neural stem/progenitor cell (hiPSC-NS/PC) transplantation for the treatment of neurodegenerative diseases and neurotraumatic injuries. In this study, we evaluated the significance of HLA matching in hiPSC-NS/PC transplantation by performing modified mixed lymphocyte reaction (MLR) assays with hiPSC-NS/PCs. Compared to fetus-derived NS/PCs, the expression levels of human leukocyte antigen-antigen D related (HLA-DR) and co-stimulatory molecules on hiPSC-NS/PCs were significantly low, even with the addition of tumor necrosis factor-α (TNFα) and/or interferon-γ (IFNγ) to mimic the inflammatory environment surrounding transplanted hiPSC-NS/PCs in injured tissues. Interestingly, both the allogeneic HLA-matched and the HLA-mismatched responses were similarly low in the modified MLR assay. Furthermore, the autologous response was also similar to the allogeneic response. hiPSC-NS/PCs suppressed the proliferative responses of allogeneic HLA-mismatched peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner. Thus, the low antigen-presenting function and immunosuppressive effects of hiPSC-NS/PCs result in a depressed immune response, even in an allogeneic HLA-mismatched setting. It is crucial to verify whether these in vitro results are reproducible in a clinical setting. |
| first_indexed | 2024-12-10T14:17:13Z |
| format | Article |
| id | doaj.art-da59fb96669e49b9b11bba585cf3a55f |
| institution | Directory Open Access Journal |
| issn | 1873-5061 |
| language | English |
| last_indexed | 2024-12-10T14:17:13Z |
| publishDate | 2017-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Research |
| spelling | doaj.art-da59fb96669e49b9b11bba585cf3a55f2022-12-22T01:45:18ZengElsevierStem Cell Research1873-50612017-03-011912813810.1016/j.scr.2017.01.007Evaluation of the immunogenicity of human iPS cell-derived neural stem/progenitor cells in vitroMasahiro Ozaki0Akio Iwanami1Narihito Nagoshi2Jun Kohyama3Go Itakura4Hiroki Iwai5Soraya Nishimura6Yuichiro Nishiyama7Soya Kawabata8Keiko Sugai9Tsuyoshi Iida10Kohei Matsubayashi11Miho Isoda12Rei Kashiwagi13Yoshiaki Toyama14Morio Matsumoto15Hideyuki Okano16Masaya Nakamura17Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan; Department of Physiology, Keio University School of Medicine, Tokyo, JapanDepartment of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, JapanDepartment of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, JapanDepartment of Physiology, Keio University School of Medicine, Tokyo, JapanDepartment of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan; Department of Physiology, Keio University School of Medicine, Tokyo, JapanDepartment of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, JapanDepartment of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, JapanDepartment of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, JapanDepartment of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, JapanDepartment of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, JapanDepartment of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, JapanDepartment of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, JapanDepartment of Physiology, Keio University School of Medicine, Tokyo, Japan; Regenerative and Cellular Medicine Office, Sumitomo Dainippon Pharma Co., Ltd., Kobe, JapanDepartment of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, JapanDepartment of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, JapanDepartment of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, JapanDepartment of Physiology, Keio University School of Medicine, Tokyo, Japan; Correspondence to: H. Okano, Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan; Correspondence to: M. Nakamura, Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.To achieve the goal of a first-in-human trial for human induced pluripotent stem cell (hiPSC)-based transplantation for the treatment of various diseases, allogeneic human leukocyte antigen (HLA)-matched hiPSC cell banks represent a realistic tool from the perspective of quality control and cost performance. Furthermore, considering the limited therapeutic time-window for acute injuries, including neurotraumatic injuries, an iPS cell bank is of potential interest. However, due to the relatively immunoprivileged environment of the central nervous system, it is unclear whether HLA matching is required in hiPSC-derived neural stem/progenitor cell (hiPSC-NS/PC) transplantation for the treatment of neurodegenerative diseases and neurotraumatic injuries. In this study, we evaluated the significance of HLA matching in hiPSC-NS/PC transplantation by performing modified mixed lymphocyte reaction (MLR) assays with hiPSC-NS/PCs. Compared to fetus-derived NS/PCs, the expression levels of human leukocyte antigen-antigen D related (HLA-DR) and co-stimulatory molecules on hiPSC-NS/PCs were significantly low, even with the addition of tumor necrosis factor-α (TNFα) and/or interferon-γ (IFNγ) to mimic the inflammatory environment surrounding transplanted hiPSC-NS/PCs in injured tissues. Interestingly, both the allogeneic HLA-matched and the HLA-mismatched responses were similarly low in the modified MLR assay. Furthermore, the autologous response was also similar to the allogeneic response. hiPSC-NS/PCs suppressed the proliferative responses of allogeneic HLA-mismatched peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner. Thus, the low antigen-presenting function and immunosuppressive effects of hiPSC-NS/PCs result in a depressed immune response, even in an allogeneic HLA-mismatched setting. It is crucial to verify whether these in vitro results are reproducible in a clinical setting.http://www.sciencedirect.com/science/article/pii/S1873506117300077iPS cell-derived neural stem/progenitor cellsHLAMixed lymphocyte reactionImmunomodulatory function |
| spellingShingle | Masahiro Ozaki Akio Iwanami Narihito Nagoshi Jun Kohyama Go Itakura Hiroki Iwai Soraya Nishimura Yuichiro Nishiyama Soya Kawabata Keiko Sugai Tsuyoshi Iida Kohei Matsubayashi Miho Isoda Rei Kashiwagi Yoshiaki Toyama Morio Matsumoto Hideyuki Okano Masaya Nakamura Evaluation of the immunogenicity of human iPS cell-derived neural stem/progenitor cells in vitro Stem Cell Research iPS cell-derived neural stem/progenitor cells HLA Mixed lymphocyte reaction Immunomodulatory function |
| title | Evaluation of the immunogenicity of human iPS cell-derived neural stem/progenitor cells in vitro |
| title_full | Evaluation of the immunogenicity of human iPS cell-derived neural stem/progenitor cells in vitro |
| title_fullStr | Evaluation of the immunogenicity of human iPS cell-derived neural stem/progenitor cells in vitro |
| title_full_unstemmed | Evaluation of the immunogenicity of human iPS cell-derived neural stem/progenitor cells in vitro |
| title_short | Evaluation of the immunogenicity of human iPS cell-derived neural stem/progenitor cells in vitro |
| title_sort | evaluation of the immunogenicity of human ips cell derived neural stem progenitor cells in vitro |
| topic | iPS cell-derived neural stem/progenitor cells HLA Mixed lymphocyte reaction Immunomodulatory function |
| url | http://www.sciencedirect.com/science/article/pii/S1873506117300077 |
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