Southern California Islet Cell Resources Center, Department of Diabetes, Endocrinology and Metabolism, Beckman Research Institute of City of Hope, Duarte, CA, USA.
Pancreas. 2011 Aug;40(6):846-54. doi: 10.1097/MPA.0b013e318215cdce.
Allogeneic mesenchymal stem cells (MSCs) and bone marrow cells (BMCs) were cotransplanted in nonobese diabetic mice after none myeloablative preconditioning and the development of chimerism, insulitis, diabetes, and graft-versus-host disease (GVHD) were monitored.
Eight-week-old female nonobese diabetic mice were injected intravenously with 2 × 10 BMCs and 5 × 10 MSCs from C57BL/6 mice after treatment with 2 intraperitoneal injections of anti-CD3 antibody (days -7 and -4) and 3-Gy 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 recipients (n = 19) and 45.0% of BMCs-alone recipients (n = 20, P = 0.256). Insulitis was prevented, and euglycemia persisted for more than 18 weeks in 89.5% of BMCs-MSCs recipients including those with less than 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 nondiabetic. Graft-versus-host disease was not detected in all mice.
Coinjection 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 microchimerism with less than 3% donor cells is sufficient for blocking autoimmunity.
在非清髓预处理后，将同种异体间充质干细胞（MSCs）和骨髓细胞（BMCs）共移植到非肥胖型糖尿病（NOD）小鼠体内，并监测嵌合体形成、胰岛炎、糖尿病和移植物抗宿主病（GVHD）的发展情况。
将 2×10^5^ C57BL/6 来源的 BMCs 和 5×10^5^ MSCs 经抗 CD3 抗体（第-7 天和-4 天）腹腔内注射 2 次和 3Gy 全身照射（第-1 天）预处理后，静脉注射 8 周龄雌性 NOD 小鼠。此后，通过外周血样本监测血糖和嵌合体形成情况。
在 BMCs-MSCs 共移植组（n=19）和 BMCs 单移植组（n=20）中，分别有 63.2%（n=19）和 45.0%（n=20）的小鼠诱导出稳定的混合嵌合体（供体表型 3-90%），两组间差异无统计学意义（P=0.256）。BMCs-MSCs 共移植组中，89.5%（n=17）的小鼠包括嵌合体小于 3%的小鼠和 55%（n=11）的 BMCs 单移植组小鼠预防了胰岛炎，并持续 18 周以上保持血糖正常，与对照组相比差异有统计学意义（P<0.05）。在对照组中，仅接受预处理治疗的小鼠有 9.1%（n=11）和仅接受 MSCs 治疗的预处理小鼠有 16.7%（n=12）未发生糖尿病。所有小鼠均未发生移植物抗宿主病。
MSC 和 BMCs 共注射可提高诱导嵌合体形成、预防胰岛炎和显性糖尿病的成功率，且无移植物抗宿主病发生。结果还表明，即使是小于 3%的供体细胞的微嵌合体也足以阻断自身免疫。
