期刊
CELL TRANSPLANTATION
卷 30, 期 -, 页码 -出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/0963689721992066
关键词
iPSCs; tumorigenicity; allogenic transplantation; MHC; cynomolgus macaque
资金
- Japan Agency for Medical Research and Development (AMED) [16bm0404007]
- Sato Yo International Scholarship Foundation
This study found that transplantation of iPSCs in MHC-matched immune-competent cynomolgus macaques did not result in tumor formation, suggesting that iPSCs may not have tumorigenicity in MHC-matched allogeneic transplantation for clinical application.
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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