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Ex-Vivo Pretreatment of Islets with Mitomycin-C Have a Potential to Induce Specific Immune Response for Peripheral Tolerance

N. Sato, A. Kenjo, T. Kimura, R. Okada, T. Ishigame, Y. Kofunato, J. Watanabe, M. Muto, S. Suzushino, T. Shimura, S. Marubashi.

Hepato-Biliary-Pancreatic and Transplant Sugery, Fukushima Medical University, Fukushima, Japan.

Meeting: 2018 American Transplant Congress

Abstract number: B80

Keywords: Immunogenicity, Islets, Tolerance

Session Information

Session Name: Poster Session B: Islet Cell and Cell Transplantation

Session Type: Poster Session

Date: Sunday, June 3, 2018

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Hall 4EF

Background.Our previous study demonstrated that ex-vivo Mitomycin-C(MMC) pretreatment of islets reduced immunogenicity, enhancing graft survival without immunosuppression(IS). However, it is still unclear whether donor specific tolerance was induced by ex-vivo MMC pretreatment. The aim of this study is to investigate an immunological mechanism to enhance graft survival of MMC-treated islets.

Methods. In transplantation examination, isolated rat islets with ex-vivo MMC pretreatment, were implanted to renal subcapsular space of diabetic mice. Immune response to xenograft in mice 4-days (n=5), 8-days (n=4), or over-100-days (n=4) after grafting was evaluated by histological analysis.

Results. Prolonged graft survival induced by ex vivo MMC treatment was determined in a concordant model of islet xeno-transplantation without IS. Histological and immunohistochemical analyses of the implant site revealed that infiltration of CD3-positive T cell was decreased in MMC-treated islets in early phase after transplantation. Interestingly, in all mice survived over-100-days, CD3-positive T cell aggregation surround by CD45R-positive B cell was found near xenograft in all mice.

Conclusion. Ex-vivo MMC pretreatment of islets reduced early phase immune response to xenograft and induced characteristic immune response in peripheral transplantation site, which may be associated with donor specific tolerance.

CITATION INFORMATION: Sato N., Kenjo A., Kimura T., Okada R., Ishigame T., Kofunato Y., Watanabe J., Muto M., Suzushino S., Shimura T., Marubashi S. Ex-Vivo Pretreatment of Islets with Mitomycin-C Have a Potential to Induce Specific Immune Response for Peripheral Tolerance Am J Transplant. 2017;17 (suppl 3).

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To cite this abstract in AMA style:

Sato N, Kenjo A, Kimura T, Okada R, Ishigame T, Kofunato Y, Watanabe J, Muto M, Suzushino S, Shimura T, Marubashi S. Ex-Vivo Pretreatment of Islets with Mitomycin-C Have a Potential to Induce Specific Immune Response for Peripheral Tolerance [abstract]. https://atcmeetingabstracts.com/abstract/ex-vivo-pretreatment-of-islets-with-mitomycin-c-have-a-potential-to-induce-specific-immune-response-for-peripheral-tolerance/. Accessed May 11, 2025.

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