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自体间充质干细胞边缘块状胰岛移植可促进胰岛同种异体移植的长期存活和持续正常血糖。

Marginal mass islet transplantation with autologous mesenchymal stem cells promotes long-term islet allograft survival and sustained normoglycemia.

作者信息

Solari Mario G, Srinivasan Suganya, Boumaza Imene, Unadkat Jignesh, Harb George, Garcia-Ocana Adolfo, Feili-Hariri Maryam

机构信息

Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.

出版信息

J Autoimmun. 2009 Mar;32(2):116-24. doi: 10.1016/j.jaut.2009.01.003. Epub 2009 Feb 12.

Abstract

Allogeneic islet transplantation is an option to treat diabetes however there are obstacles that are limiting its clinical use. We have examined whether mesenchymal stem cells (MSC) improve islet graft survival and whether such therapy allows for better graft acceptance with reduced requirement for immunosuppression. In vitro-expanded syngeneic bone marrow-derived MSC were co-transplanted with islets into omental pouch in a rat model of streptozotocin-induced diabetes. Marginal mass syngeneic islet transplantation into the omentum with MSC promoted sustained normoglycemia. Interestingly, allogeneic islets +MSC, but not islets alone, with short-term use of immunosuppression enhanced long-term islet graft survival, insulin expression in the grafts and induced normal serum insulin levels and normoglycemia. T cells from recipients transplanted with allogeneic islets +MSC produced low levels of IFN-gamma and TNF-alpha upon ex-vivo activation, and this transplantation protocol promoted the generation of IL-10-secreting CD4(+) T cells. These data encourage further preclinical and eventually, clinical MSC-based islet transplantation to improve the outcome of allogeneic islet transplantation in the treatment of diabetes.

摘要

同种异体胰岛移植是治疗糖尿病的一种选择,然而存在一些障碍限制了其临床应用。我们研究了间充质干细胞(MSC)是否能提高胰岛移植的存活率,以及这种治疗是否能在减少免疫抑制需求的情况下更好地接受移植。在链脲佐菌素诱导的糖尿病大鼠模型中,将体外扩增的同基因骨髓来源的MSC与胰岛共同移植到网膜囊中。将边缘质量的同基因胰岛与MSC移植到网膜中可促进持续的正常血糖水平。有趣的是,短期使用免疫抑制的同种异体胰岛+MSC而非单独的胰岛可提高长期胰岛移植存活率、移植中的胰岛素表达,并诱导正常的血清胰岛素水平和正常血糖。移植了同种异体胰岛+MSC的受体的T细胞在体外激活时产生低水平的IFN-γ和TNF-α,并且这种移植方案促进了分泌IL-10的CD4(+) T细胞的产生。这些数据鼓励进一步开展基于MSC的临床前研究,并最终进行临床胰岛移植,以改善同种异体胰岛移植治疗糖尿病的效果。

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