Mesenchymal stem cells facilitate the induction of mixed hematopoietic chimerism and islet allograft tolerance without GVHD in the rat
Mesenchymal stem cells facilitate the induction of mixed hematopoietic chimerism and islet allograft tolerance without GVHD in the rat
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DOI：
10.1111/j.1600-6143.2006.01643.x
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发表时间：
2007-02-01
影响因子：
8.8
通讯作者：
Mullen, Y.
中科院分区：
文献类型：
--
作者：
Itakura, S.;Asari, S.;Mullen, Y.
通过骨髓移植诱导造血嵌合体和供者特异性免疫耐受是胰岛移植治疗1型糖尿病的理想方法。我们研究了间充质干细胞（MSCs）在诱导嵌合体和胰岛移植物耐受而不发生移植物抗宿主病（GVHD）方面的潜力。链脲佐菌素糖尿病大鼠接受预处理方案，包括抗淋巴细胞血清和5戈伊全身照射，然后通过门静脉内共输注同种异体MSC，骨髓细胞（BMCs）和胰岛。尽管所有受体最初都排斥胰岛，但其中一半发展出稳定的混合嵌合体和供体特异性免疫耐受，表现为供体皮肤和第二组胰岛移植的植入以及第三方皮肤的急性排斥。通过在移植物周围添加2周的15-脱氧精胍菌素（DSG），实现了具有稳定嵌合体的原代胰岛同种异体移植物的植入。在没有MSC的情况下，接受DSG治疗的受者均未出现嵌合体或糖尿病逆转。移植物抗宿主病发生率为0/15，而未移植者发生率为4/11。这些结果表明，骨髓间充质干细胞诱导造血嵌合体和随后的免疫耐受在临床胰岛移植的潜在用途。
Induction of hematopoietic chimerism and subsequent donor-specific immune tolerance via bone marrow transplantation is an ideal approach for islet transplantation to treat type-1 diabetes. We examined the potential of mesenchymal stem cells (MSCs) in the induction of chimerism and islet allograft tolerance without the incidence of graft-versus-host disease (GVHD). Streptozotocin-diabetic rats received a conditioning regimen consisting of antilymphocyte serum and 5 Gy total body irradiation, followed by an intraportal co-infusion of allogeneic MSCs, bone marrow cells (BMCs) and islets. Although all the recipients rejected the islets initially, half of them developed stable mixed chimerism and donor-specific immune tolerance, shown by the engraftment of donor skin and second-set islet transplants and acute rejection of a third-party skin. The engraftment of the primary islet allografts with stable chimerism was achieved by the addition of a 2-week peritransplant administration of 15-deoxyspergualin (DSG). Without MSCs, none of the recipients treated with DSG developed chimerism or reversal of diabetes. GVHD was not observed in any of the recipients infused with MSCs (0/15), whereas it occurred in 4/11 recipients without MSCs. These results indicate a potential use of MSCs for induction of hematopoietic chimerism and subsequent immune tolerance in clinical islet transplantation.