Ben Nasr Moufida, Vergani Andrea, Avruch James, Liu Liye, Kefaloyianni Eirini, D'Addio Francesca, Tezza Sara, Corradi Domenico, Bassi Roberto, Valderrama-Vasquez Alessandro, Usuelli Vera, Kim James, Azzi Jamil, El Essawy Basset, Markmann James, Abdi Reza, Fiorina Paolo
Nephrology Division, Boston Children's Hospital, Harvard Medical School, Enders Building 5th Floor Room EN511, 300 Longwood Ave, Boston, MA, USA.
Transplant Medicine, Ospedale San Raffaele, Milan, Italy.
Acta Diabetol. 2015 Oct;52(5):917-27. doi: 10.1007/s00592-015-0735-y. Epub 2015 Mar 27.
Mesenchymal stem cells (MSCs) are multipotent cells with immunomodulatory properties. We tested the ability of MSCs to delay islet allograft rejection.
Mesenchymal stem cells were generated in vitro from C57BL/6 and BALB/c mice bone marrow, and their immunomodulatory properties were tested in vitro. We then tested the effect of a local or systemic administration of heterologous and autologous MSCs on graft survival in a fully allogeneic model of islet transplantation (BALB/c islets into C57BL/6 mice).
In vitro, autologous, but not heterologous, MSCs abrogated immune cell proliferation in response to alloantigens and skewed the immune response toward a Th2 profile. A single dose of autologous MSCs co-transplanted under the kidney capsule with allogeneic islets delayed islet rejection, reduced graft infiltration, and induced long-term graft function in 30 % of recipients. Based on ex vivo analysis of recipient splenocytes, the use of autologous MSCs did not appear to have any systemic effect on the immune response toward graft alloantigens. The systemic injection of autologous MSCs or the local injection of heterologous MSCs failed to delay islet graft rejection.
Autologous, but not heterologous, MSCs showed multiple immunoregulatory properties in vitro and delayed allograft rejection in vivo when co-transplanted with islets; however, they failed to prevent rejection when injected systemically. Autologous MSCs thus appear to produce a local immunoprivileged site, which promotes graft survival.
间充质干细胞（MSCs）是具有免疫调节特性的多能细胞。我们测试了间充质干细胞延缓胰岛同种异体移植排斥反应的能力。
从C57BL/6和BALB/c小鼠骨髓中体外生成间充质干细胞，并在体外测试其免疫调节特性。然后，我们在胰岛移植的完全同种异体模型（将BALB/c胰岛移植到C57BL/6小鼠体内）中测试了局部或全身给予异源和自体间充质干细胞对移植物存活的影响。
在体外，自体而非异源的间充质干细胞消除了免疫细胞对同种异体抗原的增殖反应，并使免疫反应偏向于Th2型。在肾包膜下与同种异体胰岛共移植单剂量自体间充质干细胞可延缓胰岛排斥反应，减少移植物浸润，并在30%的受体中诱导长期移植物功能。基于对受体脾细胞的体外分析，使用自体间充质干细胞似乎对针对移植物同种异体抗原的免疫反应没有任何全身影响。全身注射自体间充质干细胞或局部注射异源间充质干细胞均未能延缓胰岛移植物排斥反应。
自体而非异源的间充质干细胞在体外显示出多种免疫调节特性，并在与胰岛共移植时在体内延缓同种异体移植排斥反应；然而，当全身注射时，它们未能预防排斥反应。自体间充质干细胞因此似乎产生了一个局部免疫特惠部位，从而促进移植物存活。
