Mitomycin-C treatment followed by culture produces long-term survival of islet xenografts in a rat-to mouse model
Mitomycin-C treatment followed by culture produces long-term survival of islet xenografts in a rat-to mouse model
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DOI：
10.3727/096368908786092720
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Gotoh, Mitsukazu
中科院分区：
文献类型：
--
作者：
Gunji, Takashi;Saito, Takuro;Gotoh, Mitsukazu
胰岛移植的目标之一是在没有宿主免疫抑制的情况下移植有活力的胰岛。本研究的目的是确定是否预处理的胰岛丝裂霉素C（MMC），然后培养提高胰岛存活率在大鼠到小鼠异种组合。用不同浓度MMC（0、3.2、10、32、100、320和1000 μ g/ml）预处理WS（RT 1 k）大鼠胰岛，通过体外胰岛素分泌能力和胰岛活力染色检测其活力。将MMC处理的胰岛（10 μ g/ml）培养不同时间（4、20或40小时，3或7天）移植到STZ诱导的糖尿病C57 BL/6（36：H-2b）小鼠的肾被膜下空间。MMC处理或未处理的胰岛进行微阵列基因分析和免疫组织化学研究。体外胰岛素分泌能力和胰岛活体染色的评价表明，当10 μ g/ml MMC处理的胰岛在培养40小时或3天后移植时，MMC剂量为100天，但当它们在处理后4小时内或处理后7天内移植时，MMC剂量为100天，表明存在成功的胰岛移植物存活所必需的关键培养期。微阵列分析表明，这种延长与TGF-β高表达MMC处理的胰岛进行培养3天的可能基因。我们的研究结果表明，MMC治疗后的一个关键的文化时期诱导显着延长大鼠胰岛异种移植物在nonimmunosuppressed受体小鼠的生存，提供了一个策略，胰岛移植无免疫抑制。
One of the goals of islet transplantation is to transplant viable islets without host immunosuppression. The present study was designed to determine whether pretreatment of islets with mitomycin-C (MMC) followed by culture enhances islet survival in a rat-to-mouse xenogeneic combination. WS(RT1k) rat islets pretreated with various concentrations of MMC (0, 3.2, 10, 32, 100, 320, and 1000 mu g/ml) were tested for viability by in vitro insulin secretory capacity and vital staining of islets. The MMC-treated islets (10 mu g/ml) cultured for various periods (4, 20, or 40 h, 3 or 7 days) were transplanted into the renal subcapsular space of STZ-induced diabetic C57BL/6 (36: H-2b) mice. MMC-treated or nontreated islets were subjected to microarray gene analysis and immunohistological study. Evaluation of in vitro insulin secretory capacity and vital staining of islets indicated that MMC at a dose 100 days) when 10 mu g/ml of MMC-treated islets was transplanted after 40 h or 3 days in culture, but not when they were transplanted within 4 h following treatment or at 7 days following treatment, indicating that there is a critical culture period necessary for successful islet graft survival. Microarray analysis suggested possible genes for this prolongation with TGF-beta highly expressed in MMC-treated islets subjected to culture for 3 days. Our results indicate that MMC treatment followed by a critical culture period induces marked prolongation of rat islet xenograft survival in nonimmunosuppressed recipient mice, offering a strategy for islet transplantation without immunosuppression.