Adult porcine islet transplantation in baboons treated with conventional immunosuppression or a non-myeloablative regimen and CD154 blockade
Adult porcine islet transplantation in baboons treated with conventional immunosuppression or a non-myeloablative regimen and CD154 blockade
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DOI：
10.1034/j.1399-3089.2002.1o044.x
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发表时间：
2002-01-01
影响因子：
3.9
通讯作者：
Morel, P
中科院分区：
文献类型：
--
作者：
Bühler, L;Deng, S;Morel, P
本研究的目的是评估将成年猪胰岛移植到狒狒体内，接受(1)常规三联免疫抑制药物治疗或(2)非清髓方案和旨在诱导耐受的抗cd154单克隆抗体（mAb）的存活率。第1组狒狒（n=3）在门静脉注射10000猪胰岛当量(IE)/kg前切除胰腺，并用抗胸腺细胞球蛋白（ATG）、环孢素和硫唑嘌呤进行免疫抑制。在第二组（n=2）中，未切除胰腺的狒狒接受全身和胸腺照射和ATG诱导治疗。采用体外免疫吸附法（EIA）检测抗galphalalal，3Gal （Gal）抗体。维持治疗采用眼镜蛇毒因子、环孢素、霉酚酸酯、甲基强的松龙和抗cd154单抗。猪胰岛静脉注射（分别为14000和32000 IE/kg），全身静脉注射高剂量的猪动员外周血祖细胞（3 × 10（10）个细胞/kg）。猪胰岛也被植入胸锁乳突肌，以方便随后的活检。两组均检测猪c肽，定期进行肝脏组织学检查或胸锁乳突肌活检。在组1中，全胰切除术使人c肽减少到14天。然而，尽管T细胞消耗殆尽。抗gal抗体和补体，以及cd154阻断剂。猪胰岛在第28天被排斥。这些结果表明，强大的先天免疫反应参与排斥不一致的异种胰岛。
The aim of the present study was to assess the survival of adult porcine islets transplanted into baboons receiving either (1) conventional triple drug immunosuppressive therapy or (2) a non-myeloablative regimen and an anti-CD154 monoclonal antibody (mAb) aimed at tolerance-induction.Group 1 baboons (n=3) were pancreatectomized prior to intraportal injection of 10 000 porcine islet equivalents (IE)/kg and immunosuppressed with anti-thymocyte globulin (ATG), cyclosporine and azathioprine. In Group 2 (n=2), non-pancreatectomized baboons underwent induction therapy with whole body and thymic irradiation, and ATG.Extracorporeal immunoadsorption (EIA) of anti-Galphalalphal,3Gal (Gal) antibody was carried out. Maintenance therapy was with cobra venom factor, cyclosporine, mycophenolate mofetil, methylprednisolone and anti-CD154 mAb. Porcine islets were injected intraportally (14 000 and 32 000 IE/kg, respectively) and high-dose pig mobilized peripheral blood proigenitor cells (3 x 10(10) cells/kg) were infused into a systemic vein. Porcine islets were also implanted in the sternomastoid muscle to facilitate subsequent biopsies. In both groups, porcine C-peptide was measured, and histological examination of liver or sternomastoid muscle biopsies was performed at regular intervals.In Group 1, total pancreatectomy reduced human C-peptide to 14 days. However, despite depletion of T cells. anti-Gal antibody and complement, and CD154-blockade. porcine islets were rejected by day 28. These results suggest that powerful innate immune responses are involved in rejection of discordant xenogeneic islets.