Assessing the effect of immunosuppression on engraftment of pancreatic islets.
Assessing the effect of immunosuppression on engraftment of pancreatic islets.
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评估免疫抑制对胰岛植入的影响。
DOI：
10.1097/tp.0b013e31829f7515
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发表时间：
2013
期刊：
影响因子：
6.2
通讯作者：
Sachs,DavidH
中科院分区：
文献类型：
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作者：
Vallabhajosyula,Prashanth;Hirakata,Atsushi;Shimizu,Akira;Okumi,Masayoshi;Tchipashvili,Vaja;Hong,Hanzhou;Yamada,Kazuhiko;Sachs,DavidH
背景除了缺血和免疫因素外，免疫抑制剂也被认为是同种异体胰岛细胞移植后功能性胰岛丧失的一个可能因素。使用我们以前描述的胰岛肾（IK）移植模型在小型猪，我们研究了是否胰岛毒性三联药物免疫抑制方案（环孢素+硫唑嘌呤+泼尼松）影响胰岛移植过程，从而长期的胰岛function.MethodsDonor动物进行部分胰腺切除术，自体胰岛制备，并注射这些胰岛下的自体肾包膜，以制备IK。在胰岛移植期间，实验动物每天接受三联药物免疫抑制。对照动物在此期间未接受任何免疫抑制。4 - 8周后，这些移植的IK以约4500胰岛当量/kg受体重量的胰岛剂量穿过轻微的组织相容性不匹配的屏障移植到胰腺切除、肾切除的受体动物中。环孢素给药12天的收件人诱导耐受的IK移植物和动物进行了长期的。ResultsDiabetes纠正IK移植在所有pancreatectomized收件人的对照组（n= 3）和实验组（n= 4）的研究和所有动物在随访期间显示正常的葡萄糖调节。在IK移植后1，2，3个月或更多个月进行的静脉葡萄糖耐量试验显示，在控制和实验animals.ConclusionIn此临床前在体内胰岛移植的大动物模型，三重药物免疫抑制对胰岛功能的影响并没有负面影响胰岛移植评估的长期功能移植胰岛。
BackgroundIn addition to ischemia and immunologic factors, immunosuppressive drugs have been suggested as a possible contributing factor to the loss of functional islets after allogeneic islet cell transplantation. Using our previously described islet-kidney (IK) transplantation model in miniature swine, we studied whether an islet-toxic triple-drug immunosuppressive regimen (cyclosporine+ azathioprine+ prednisone) affects the islet engraftment process and thus long-term islet function.MethodsDonor animals underwent partial pancreatectomy, autologous islet preparation, and injection of these islets under the autologous kidney capsule to prepare an IK. Experimental animals received daily triple-drug immunosuppression during the islet engraftment period. Control animals did not receive any immunosuppression during this period. Four to 8 weeks later, these engrafted IK were transplanted across a minor histocompatibility mismatched barrier into pancreatectomized, nephrectomized recipient animals at an islet dose of approximately 4500 islet equivalents/kg recipient weight. Cyclosporine was administered for 12 days to the recipients to induce tolerance of the IK grafts and the animals were followed long-term.ResultsDiabetes was corrected by IK transplantation in all pancreatectomized recipients on both the control arm (n= 3) and the experimental arm (n= 4) of the study and all animals showed normal glucose regulation over the follow-up period. Intravenous glucose tolerance tests performed at 1, 2, and 3 or more months after IK transplantation showed essentially equivalent glycemic control in both control and experimental animals.ConclusionIn this preclinical in vivo large animal model of islet transplantation, the effect of triple-drug immunosuppression on islet function does not negatively affect islet engraftment as assessed by the long-term function of engrafted islets.