Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Mol Ther. 2013 Sep;21(9):1778-86. doi: 10.1038/mt.2013.147. Epub 2013 Jun 14.
Human islet transplantation can be a permanent treatment of type 1 diabetes if the immune rejection and primary nonfunction (PNF) of transplanted islet grafts were properly addressed. In this study, we determined whether cotransplantation of human bone marrow-derived mesenchymal stem cells (hBMSCs) could prevent immune rejection and improve human islet transplantation in a humanized NOD scid gamma (NSG) mouse model. Human immunity was rebuilt and maintained in NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ (NSG) mice up to 13 weeks after intraperitoneal injection of mature human peripheral blood mononuclear cells (PBMCs). The blood glucose control and the levels of serum insulin and c-peptide clearly indicated a better outcome of islet transplantation when islets were cotransplanted with hBMSCs. hBMSCs actively interacted with interleukin-10 (IL-10)-producing CD14+ monocytes to suppress the proliferation and activation of T cells in the PBMC/hBMSC coculture and prevent the T cell recruitment into the transplantation site. hBMSCs also increased the percentage of immunosuppressive regulatory T cells (Tregs) and prevented the cytokine-induced loss-of-function of human islets. Taken together, our studies demonstrated that transplantation of islets with hBMSCs is a promising strategy to improve the outcome of human islet transplantation.
如果能够妥善解决免疫排斥和移植胰岛原发性无功能（PNF）问题，人胰岛移植可以成为 1 型糖尿病的一种永久性治疗方法。在这项研究中，我们确定了在人源化 NOD scid 伽马（NSG）小鼠模型中，共移植人骨髓间充质干细胞（hBMSCs）是否可以预防免疫排斥并改善人胰岛移植。通过腹腔内注射成熟的人外周血单核细胞（PBMCs），在 NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ（NSG）小鼠中重建和维持人类免疫长达 13 周。当胰岛与 hBMSCs 共移植时，血糖控制以及血清胰岛素和 C 肽水平明显表明胰岛移植的效果更好。hBMSCs 与产生白细胞介素 10（IL-10）的 CD14+单核细胞积极相互作用，抑制 PBMC/hBMSC 共培养中 T 细胞的增殖和活化，并防止 T 细胞募集到移植部位。hBMSCs 还增加了免疫抑制调节性 T 细胞（Tregs）的比例，并防止细胞因子诱导的人胰岛功能丧失。总之，我们的研究表明，与 hBMSCs 共移植胰岛是改善人胰岛移植效果的一种有前途的策略。
