Mesenchymal stem cells facilitate mixed hematopoietic chimerism induction and prevent onset of diabetes in nonobese diabetic mice.
Mesenchymal stem cells facilitate mixed hematopoietic chimerism induction and prevent onset of diabetes in nonobese diabetic mice.
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DOI：
10.1097/mpa.0b013e318215cdce
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发表时间：
2011-08
期刊：
影响因子：
2.9
通讯作者：
Mullen YS
中科院分区：
文献类型：
--
作者：
Asari S;Itakura S;Rawson J;Ito T;Todorov I;Nair I;Shintaku J;Liu CP;Kandeel F;Mullen YS
同种异体间充质干细胞（MSCs）和骨髓细胞（BMCs）在未进行清髓预处理的NOD小鼠中共移植，并监测嵌合、胰岛素、糖尿病和移植物抗宿主病（GVHD）的发展。8周龄雌性NOD小鼠经2次腹腔注射抗cd3抗体（- 7和- 4天）和3Gy全身照射（- 1天）后，静脉注射C57BL/6小鼠的2×107 BMCs和5×105 MSCs。随后，监测外周血样本的血糖和嵌合情况。63.2%的BMCs- mscs -受体（n=19）和45.0%的BMCs单独受体（n=20, p=0.256）诱导了稳定的混合嵌合（3- bb0 - 90%的供体表型）。89.5%的骨髓基质-间充质干细胞受体（包括嵌合率<3%的受体）和55%的骨髓基质-间充质干细胞受体（p<0.05）可预防胰岛素炎，血糖维持正常（p<0.05）。在对照组中，9.1%单独接受预处理的小鼠（n=11）和16.7%仅接受MSCs预处理的小鼠（n=12）非糖尿病。所有小鼠均未检测到GVHD。骨髓间充质干细胞和骨髓间充质干细胞联合注射可提高诱导嵌合的成功率，预防无GVHD发生的胰岛素和显性糖尿病。结果还表明，即使与小于3%的供体细胞嵌合也足以阻断自身免疫。
Allogeneic mesenchymal stem cells (MSCs) and bone marrow cells (BMCs) were co-transplanted in NOD mice following none myeloablative preconditioning and the development of chimerism, insulitis, diabetes, and graft versus host disease (GVHD) were monitored. Eight-weeks-old female NOD mice were injected intravenously with 2×107 BMCs and 5×105 MSCs from C57BL/6 mice following treatment with 2 intraperitoneal injections of anti-CD3 antibody (days −7 and −4), and 3Gy total body irradiation (day −1). Thereafter, blood glucose and chimerism were monitored on peripheral blood samples. Stable mixed chimerism (3->90% of donor phenotype) was induced in 63.2% of BMCs-MSCs-(n=19) and 45.0% of BMCs alone recipients (n=20, p=0.256). Insulitis was prevented and euglycemia persisted for >18 weeks in 89.5% of BMCs-MSCs recipients including those with <3% chimerism and 55% of BM alone recipients (p<0.05). In controls, 9.1% of mice receiving preconditioning treatment alone (n=11) and 16.7% of preconditioned mice receiving only MSCs (n=12) were non-diabetic. GVHD was not detected in all mice. Co-injection of MSCs and BMCs increased the success rate in inducing chimerism and preventing insulitis and overt diabetes with no incidence of GVHD. Results also indicated that even micro-chimerism with <3% donor cells is sufficient for blocking autoimmunity.