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胰岛与间质干细胞共移植对 T 和树突状细胞的免疫调节。

Immune modulation of co-transplantation mesenchymal stem cells with islet on T and dendritic cells.

机构信息

Clinical Medical Research Center, the Second Clinical Medical College (Shenzhen People's Hospital) Ji'nan University, Shenzhen, China.

出版信息

Clin Exp Immunol. 2010 Aug;161(2):357-63. doi: 10.1111/j.1365-2249.2010.04178.x. Epub 2010 May 7.

DOI:10.1111/j.1365-2249.2010.04178.x
PMID:20456412
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2909419/
Abstract

Allogeneic pancreatic islet transplantation theoretically represents a cure for type 1 diabetes. However, current immune suppressive therapies are often associated with undesired side effects. Given this problem, and the shortage of human islet donors, the majority of type 1 diabetes patients cannot currently be offered an islet transplant. However, it has been found that mesenchymal stem cells (MSCs) could exert unique immunosuppressive effects both in vitro and in vivo. Herein we transplanted allogeneic 200 islets alone or in combination with MSCs (3 x 10(6) cells) under the kidney capsules of diabetic C57LB/6 mouse. We found that the ratios of T helper type 1 (Th1) to Th2 and Tc1 to Tc2 were reduced, and the numbers of naive and memory T cells were down-regulated in peripheral blood after transplantation. In addition, the maturation, endocytosis and interleukin-12 secretion of dendritic cell (DCs)-derived bone marrow cells (BMCs) from receptor mice were suppressed. Rejection reaction was alleviated by MSCs which exerted suppressive effects through T lymphocyte subsets and DCs.

摘要

同种异体胰岛移植理论上代表了 1 型糖尿病的一种治愈方法。然而,目前的免疫抑制疗法常常伴有不良的副作用。鉴于这一问题和胰岛供体的短缺,大多数 1 型糖尿病患者目前无法接受胰岛移植。然而,已经发现间充质干细胞 (MSCs) 在体外和体内都能发挥独特的免疫抑制作用。在此,我们将同种异体 200 个胰岛单独或与 MSCs(3 x 10(6) 个细胞)一起移植到糖尿病 C57LB/6 小鼠的肾脏包膜下。我们发现,移植后外周血中辅助性 T 细胞 1 (Th1) 与 Th2 和 Tc1 与 Tc2 的比值降低,幼稚和记忆 T 细胞的数量减少。此外,受体小鼠来源的树突状细胞 (DCs) 骨髓细胞 (BMCs) 的成熟、内吞和白细胞介素-12 分泌受到抑制。MSCs 通过 T 淋巴细胞亚群和 DCs 发挥抑制作用,减轻了排斥反应。

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Eur J Immunol. 2009 Sep;39(9):2325-30. doi: 10.1002/eji.200939548.
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Bone marrow-derived mesenchymal stem cells improve islet graft function in diabetic rats.骨髓间充质干细胞改善糖尿病大鼠胰岛移植功能。
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Combinations of growth factors enhance the potency of islets in vitro.生长因子的组合可增强胰岛在体外的效力。
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Marginal mass islet transplantation with autologous mesenchymal stem cells promotes long-term islet allograft survival and sustained normoglycemia.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。
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Current status of islet cell transplantation.胰岛细胞移植的现状
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Autologous bone marrow-derived rat mesenchymal stem cells promote PDX-1 and insulin expression in the islets, alter T cell cytokine pattern and preserve regulatory T cells in the periphery and induce sustained normoglycemia.自体骨髓来源的大鼠间充质干细胞可促进胰岛中PDX-1和胰岛素的表达,改变T细胞细胞因子模式,在外周保留调节性T细胞,并诱导持续正常血糖。
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Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population.间充质干细胞诱导成熟树突状细胞分化为一种新型的依赖Jagged-2的调节性树突状细胞群体。
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Co-infusion of donor bone marrow with host mesenchymal stem cells treats GVHD and promotes vascularized skin allograft survival in rats.供体骨髓与宿主间充质干细胞共同输注可治疗移植物抗宿主病并促进大鼠血管化皮肤同种异体移植的存活。
Clin Immunol. 2008 Jun;127(3):348-58. doi: 10.1016/j.clim.2008.02.003. Epub 2008 Apr 2.