期刊
TRANSPLANTATION
卷 86, 期 1, 页码 46-53出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TP.0b013e31817c79c0
关键词
islet; transplantation; rapamycin; cytokine; chemokine
资金
- NCRR NIH HHS [U42 RR016603-01, U42 RR016603, IU42RR016603, U42 RR016603-08, U42 RR016603-03, U42 RR016603-075798, U42 RR016603-058063, U42 RR016603-048770, U42 RR016603-060001, U42 RR016603-07, U42 RR016603-05S1, U42 RR016603-03S1, U42 RR016603-04S1, U42 RR016603-04, M01 RR016587, U42 RR016603-087487, 5U42RR016603, U42 RR016603-06, U42 RR016603-05, U42 RR016603-06S1, U42 RR016603-02, M01RR16587] Funding Source: Medline
- NIDDK NIH HHS [R01 DK025802-19, R01-DK55347, R01 DK025802, R01 DK025802-20, R01 DK055347-03, R01 DK055347-02, 5R01 DK25802] Funding Source: Medline
Background. Sirolimus plays a critical role in facilitating steroid-free immunosuppression, in conjunction with low dose tacrolimus, in current islet transplantation. Although several studies have investigated the effects of sirolimus on islet cells, conflicting results have been reported. In this study, we assessed the effects of sirolimus supplementation in culture media on human islet preparations, focusing on the anti-proinflammatory aspects. Methods. Human islet preparations were divided into four groups: pure (purity >90%) sirolimus (30 ng/mL); pure control (0 ng/mL); impure (purity 40%-60%) sirolimus; and impure control. All groups were cultured for 3 days and assessed regarding glucose stimulated insulin release, fractional beta-cell viability, beta-cell, and macrophage content. Cytokine and chemokine production from islet preparations and sorted pancreatic ductal cells were also examined. Results. Stimulated insulin release in the impure sirolimus group was significantly increased (P=0.024), as previously reported. Although fractional beta-cell viability showed no significant differences, beta-cell survival during culture significantly increased in impure sirolimus group when compared with the impure control group (P=0.015). Tumor necrosis factor-alpha, interleukin-1 beta, monocyte chemotactic protein-1, and macrophage inflammatory protein-1 beta production from the impure sirolimus group significantly decreased (P<0.05). Furthermore, tumor necrosis factor-alpha and macrophage inflammatory protein-1 beta production from sorted ductal cells significantly decreased in the sirolimus group (P<0.05). The number of macrophages contained in islet preparations significantly decreased in the impure sirolimus group when compared with the impure control group (P<0.05). Conclusions. Sirolimus improved not only stimulated insulin release, but also beta-cell survival during culture. The antiinflammatory effects of sirolimus also appear beneficial to islet cells in culture and may be a useful strategy in improving islet transplantation outcomes.
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