目的观察间充质干细胞(MSC)联合骨髓细胞(BMC)输注对同种异体小鼠胰岛移植嵌合状态及胰岛移植物存活时间的影响。方法C57BL/6小鼠和BALB/C小鼠分别作为供、受体。应用链脲佐菌素制备BALB/C小鼠糖尿病模型,将分离纯化的C57BL/6小鼠胰岛移植到上述糖尿病模型小鼠的肾包囊下,用抗CD154单抗进行受体预处理。将接受胰岛移植的25只BALB/C受体鼠随机分为A组(单纯胰岛移植);B组(供体MSC悬液0.5ml输注);C组(供体BMC悬液0.5ml输注);D组(供体BMC和MSC各0.5ml输注);E组(供体BMC和第三品系的KM小鼠MSC各0.5ml输注),每组5只,所有细胞在胰岛移植后经尾静脉输注。比较以上各组供体细胞嵌合率(DC)和胰岛移植物存活时间的差异。结果在胰岛移植后第30天,MSC联合BMC输注的D、E两组与单纯BMC输注的C组比较,其DC显著升高(P〈0.01);胰岛存活时间亦显著延长[(77.0±7.7d)和(61.0±2.2d)vs(53.0±16.4d)(P〈0.01)]。胰岛移植后第60天,D组与E组比较,DC维持在更高水平,且胰岛移植物存活时间更长(P〈0.05)。结论MSC联合BMC输注比单纯BMC输注能够维持更长时间的混合嵌合状态,并延长胰岛移植物存活时间;供体来源的MSC输注比非供体来源的MSC输注更有效。
Objective To examine the effects of mixed infusion of mesenchymal stem cells (MSCs) and bone marrow cells (BMCs) in the induction of chimerism and islet allograft tolerance. Methods BALB/C mouse was used as the recipient and C57BL/6 mouse was as the donor. BALB/C mice were rendered diabetic via injection of streptozotocin. The islet cells of donor mice were transplanted into the recipient mice under the capsule of kidney. Rat anti-mouse CD154 mAb was intraperitoneaUy injected to the recipient mice. All of recipient mice ( n= 25 ) were then randomly divided into five groups: A group ( received nothing), B group (donor MSCs), C group ( donor BMCs), D group (donor BMCs and MSCs) and E group (donor BMCs and the third strain-derived MSCs). The chimerism level of donor cells and the survival time of islet grafts were compared among these five groups on 7, 30d and 60d after transplantation. Results On 30d and 60d after islet transplantation, the chimerism levels of donor cells in D and E groups, in which the recipient mice received the mixed infusion of MSCs and BMCs, were significantly higher than that in C group, in which the recipient mice received BMCs infusion only, and the survival time of islet graft prolonged from 53. 0±16. 4d to 77. 0±7.7d and 61. 0±2. 2d, respectively (P〈0. 01). On 60d after islet transplantation, the donor chimerism level was obviously higher than that in E group. The survival time of islet grafts in D group was also significantly longer than that in E group. Conclusion Mixed infusion of MSCs and BMCs facilitates the induction of mixed chimerism and long-term survival of islet allograft. The donor-derived MSCs infusion is more effective than that of the third strain-derived MSCs infusion.