(Secondary Publication)Tacrolimusが移植膵島の血管再構築へ及ぼす影響  [in Japanese] (Secondary Publication)Tacrolimus inhibits the revascularization of isolated pancreatic islets  [in Japanese]

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    • 里見 進 SATOMI Susumu
    • 東北大学大学院先進外科学分野 Division of Advanced Surgical Science and Technology, Tohoku University
    • 後藤 昌史 GOTO Masafumi
    • 東北大学大学院先進外科学分野|東北大学未来科学技術共同研究センター Division of Advanced Surgical Science and Technology, Tohoku University|New Industry Creation Hatchery Center, Tohoku University
    • 西岡 翔 NISHIOKA Sho
    • 東北大学大学院環境科学研究科 Graduate School of Environmental Studies, Tohoku University
    • 牛山 明 USHIYAMA Akira
    • 国立保健医療科学院生活環境研究部 Department of Environmental Health, National Institute of Public Health


【<b>Objective】</b>Immunosuppressive drugs could be crucial factors for a poor outcome after islet allotransplantation. Unlike rapamycin, the effects of tacrolimus, the current standard immunosuppressant used in islet transplantation, on graft revascularization remain unclear. We examined the effects of tacrolimus on islet revascularization using a highly sensitive imaging system, and analyzed the gene expression in transplanted islets by introducing laser microdissection techniques.<br>【<b>Methods】</b>Islets isolated from C57BL/6-Tg (CAG-EGFP) mice were transplanted into the nonmetallic dorsal skinfold chamber on the recipients. Balb/c athymic mice were used as recipients and divided into two groups, including a control group (n=9) and tacrolimus-treated group (n=7). Changes in the newly-formed vessels surrounding the islet grafts were imaged and semi-quantified using multi-photon laser-scanning microscopy and a Volocity system. Gene expression in transplanted islets was analyzed by the BioMark dynamic system.<br>【<b>Results】</b>The revascularization process was completed within 14 days after pancreatic islet transplantation at subcutaneous sites. The newly-formed vascular volume surrounding the transplanted islets in the tacrolimus-treated group was significantly less than that in the control group (p<0.05). Although the expression of <i>Vegfa</i> (p<0.05) and <i>Ccnd1</i> (p<0.05) was significantly upregulated in the tacrolimus-treated group compared with that of the control group, no differences were observed between the groups in terms of other types of gene expression.<br>【<b>Conclusion】</b>The present study demonstrates that tacrolimus inhibits the revascularization of isolated pancreatic islets without affecting the characteristics of the transplanted grafts. Further refinements of this immunosuppressive regimen, especially regarding the revascularization of islet grafts, could improve the outcome of islet allotransplantation.<br>*This article is a secondary publication in Japanese of "Tacrolimus inhibits the revascularization of isolated pancreatic islets" published by Nishimura R, Nishioka S, Fujisawa I, <i>et al</i>. PLoS One.2013 Apr 17; 8. DOI: 10.1371/journal.pone.56799


  • Japanese Journal of Transplantation

    Japanese Journal of Transplantation 49(4-5), 353-362, 2014

    The Japan Society for Transplantation


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