Tacrolimus Inhibits the Revascularization of Isolated Pancreatic Islets

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Apr 25

PMID 23613708

Citations 18

Authors

Ryuichi Nishimura

Sho Nishioka

Ikuma Fujisawa

Hitoshi Shiku

Miki Shimada

Satoshi Sekiguchi

Keisei Fujimori

Akira Ushiyama

Tomokazu Matsue

Noriaki Ohuchi

Susumu Satomi

Masafumi Goto

Affiliations

Soon will be listed here.

Abstract

Aims: 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.

Methods: 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 were divided into two groups: including a control group (n = 9) and tacrolimus-treated group (n = 7). The 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.

Results: 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 Vegfa (p<0.05) and Ccnd1 (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.

Conclusions: 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.

Citing Articles

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A gelatin hydrogel nonwoven fabric improves outcomes of subcutaneous islet transplantation.

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Ideal Duration of Pretreatment Using a Gelatin Hydrogel Nonwoven Fabric Prior to Subcutaneous Islet Transplantation.

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