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No Tumorigenicity of Allogeneic Induced Pluripotent Stem Cells in Major Histocompatibility Complex-matched Cynomolgus Macaques.
Cell Transplant. 2021 Jan-Dec; 30:963689721992066.CT

Abstract

Tumorigenicity of induced pluripotent stem cells (iPSCs) is anticipated when cells derived from iPSCs are transplanted. It has been reported that iPSCs formed a teratoma in vivo in autologous transplantation in a nonhuman primate model without immunosuppression. However, there has been no study on tumorigenicity in major histocompatibility complex (MHC)-matched allogeneic iPSC transplantation with immune-competent hosts. To examine the tumorigenicity of allogeneic iPSCs, we generated four iPSC clones carrying a homozygous haplotype of the MHC. Two clones were derived from female fibroblasts by using a retrovirus and the other two clones were derived from male peripheral blood mononuclear cells by using Sendai virus (episomal approach). The iPSC clones were transplanted into allogenic MHC-matched immune-competent cynomolgus macaques. After transplantation of the iPSCs into subcutaneous tissue of an MHC-matched female macaque and into four testes of two MHC-matched male macaques, histological analysis showed no tumor, inflammation, or regenerative change in the excised tissues 3 months after transplantation, despite the results that iPSCs formed teratomas in immune-deficient mice and in autologous transplantation as previously reported. The results in the present study suggest that there is no tumorigenicity of iPSCs in MHC-matched allogeneic transplantation in clinical application.

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Publisher Full Text
ncbi.nlm.nih.gov
journals.sagepub.com
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Authors+Show Affiliations

Ishigaki H
Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Pham VL
Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan. Biomolecular and Genetic Unit, Department of Hematology, Choray Hospital, Ho Chi Minh City, Vietnam.
Terai J
Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Sasamura T
Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Nguyen CT
Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Ishida H
Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Okahara J
Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan.
Kaneko S
Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
Shiina T
Division of Basic Medical Science and Molecular Medicine, Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Nakayama M
Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Itoh Y
Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Ogasawara K
Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan.

MeSH

AnimalsCarcinogenesisFemaleHematopoietic Stem Cell TransplantationInduced Pluripotent Stem CellsMacaca fascicularisMajor Histocompatibility ComplexMaleTransplantation, Homologous

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33588604

Citation

Ishigaki, Hirohito, et al. "No Tumorigenicity of Allogeneic Induced Pluripotent Stem Cells in Major Histocompatibility Complex-matched Cynomolgus Macaques." Cell Transplantation, vol. 30, 2021, p. 963689721992066.
Ishigaki H, Pham VL, Terai J, et al. No Tumorigenicity of Allogeneic Induced Pluripotent Stem Cells in Major Histocompatibility Complex-matched Cynomolgus Macaques. Cell Transplant. 2021;30:963689721992066.
Ishigaki, H., Pham, V. L., Terai, J., Sasamura, T., Nguyen, C. T., Ishida, H., Okahara, J., Kaneko, S., Shiina, T., Nakayama, M., Itoh, Y., & Ogasawara, K. (2021). No Tumorigenicity of Allogeneic Induced Pluripotent Stem Cells in Major Histocompatibility Complex-matched Cynomolgus Macaques. Cell Transplantation, 30, 963689721992066. https://doi.org/10.1177/0963689721992066
Ishigaki H, et al. No Tumorigenicity of Allogeneic Induced Pluripotent Stem Cells in Major Histocompatibility Complex-matched Cynomolgus Macaques. Cell Transplant. 2021 Jan-Dec;30:963689721992066. PubMed PMID: 33588604.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - No Tumorigenicity of Allogeneic Induced Pluripotent Stem Cells in Major Histocompatibility Complex-matched Cynomolgus Macaques. AU - Ishigaki,Hirohito, AU - Pham,Van Loi, AU - Terai,Jun, AU - Sasamura,Takako, AU - Nguyen,Cong Thanh, AU - Ishida,Hideaki, AU - Okahara,Junko, AU - Kaneko,Shin, AU - Shiina,Takashi, AU - Nakayama,Misako, AU - Itoh,Yasushi, AU - Ogasawara,Kazumasa, PY - 2021/2/16/entrez PY - 2021/2/17/pubmed PY - 2021/11/18/medline KW - MHC KW - allogenic transplantation KW - cynomolgus macaque KW - iPSCs KW - tumorigenicity SP - 963689721992066 EP - 963689721992066 JF - Cell transplantation JO - Cell Transplant VL - 30 N2 - Tumorigenicity of induced pluripotent stem cells (iPSCs) is anticipated when cells derived from iPSCs are transplanted. It has been reported that iPSCs formed a teratoma in vivo in autologous transplantation in a nonhuman primate model without immunosuppression. However, there has been no study on tumorigenicity in major histocompatibility complex (MHC)-matched allogeneic iPSC transplantation with immune-competent hosts. To examine the tumorigenicity of allogeneic iPSCs, we generated four iPSC clones carrying a homozygous haplotype of the MHC. Two clones were derived from female fibroblasts by using a retrovirus and the other two clones were derived from male peripheral blood mononuclear cells by using Sendai virus (episomal approach). The iPSC clones were transplanted into allogenic MHC-matched immune-competent cynomolgus macaques. After transplantation of the iPSCs into subcutaneous tissue of an MHC-matched female macaque and into four testes of two MHC-matched male macaques, histological analysis showed no tumor, inflammation, or regenerative change in the excised tissues 3 months after transplantation, despite the results that iPSCs formed teratomas in immune-deficient mice and in autologous transplantation as previously reported. The results in the present study suggest that there is no tumorigenicity of iPSCs in MHC-matched allogeneic transplantation in clinical application. SN - 1555-3892 UR - https://www.unboundmedicine.com/medline/citation/33588604/No_Tumorigenicity_of_Allogeneic_Induced_Pluripotent_Stem_Cells_in_Major_Histocompatibility_Complex_matched_Cynomolgus_Macaques_ L2 - https://journals.sagepub.com/doi/10.1177/0963689721992066?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -