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大学・研究所にある論文を検索できる 「Mitomycin C treatment improves pancreatic islet graft longevity in intraportal islet transplantation by suppressing proinflammatory response」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。
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Mitomycin C treatment improves pancreatic islet graft longevity in intraportal islet transplantation by suppressing proinflammatory response

Yamane, Kei 京都大学 DOI:10.14989/doctor.k22884

2021.01.25

概要

The in vitro culture period prior to cell transplantation (i.e. pancreatic islet transplantation) enables cell modifcation and is thus advantageous. However, the islet preconditioning method has not been fully explored. Here we present a simple approach for islet preconditioning that uses the antibiotic mitomycin C (MMC), which has antitumor activity, to reduce islet immunogenicity and prevent proinfammatory events in an intraportal islet transplantation model. Freshly isolated mice islets were treated for 30 min with 10 μg/mL MMC or not, cultured for 20 h and transplanted into the livers of syngeneic or allogeneic diabetic mouse recipients. In the allogeneic model, MMC preconditioning signifcantly prolonged graft survival without requiring immunosuppressants. In vitro, MMC treatment suppressed the expression of proinfammatory cytokines in islet allografts, while immunohistochemical studies revealed the suppression of infammatory cell infltration into MMCtreated allografts relative to untreated allografts. Furthermore, MMC preconditioning signifcantly suppressed the mRNA expression of proinfammatory cytokines into the transplant site and induced the diferentiation of regulatoryT cells with the ability to suppress ¬CD4+T cell-mediated immune responses. In conclusion, islet preconditioning with MMC prolonged graft survival in an intraportal islet transplantation model by suppressing proinfammatory events and inducing potentially regulatory lymphocytes.

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