Mesenchymal Stem Cells Prolong Composite Tissue Allotransplant Survival in a Swine Model
Mesenchymal Stem Cells Prolong Composite Tissue Allotransplant Survival in a Swine Model
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DOI：
10.1097/tp.0b013e3181a664f1
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发表时间：
2009-06-27
期刊：
影响因子：
6.2
通讯作者：
Lee, W. P. Andrew
中科院分区：
文献类型：
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作者：
Kuo, Yur-Ren;Goto, Shigeru;Lee, W. P. Andrew
背景本研究探讨了间充质干细胞（MSCs）联合骨髓移植（BMT）、放疗或短期免疫抑制剂治疗是否能延长猪后肢复合组织同种异体移植物的存活时间。在远交小型猪中进行异位后肢移植。I组（n=5）为未处理对照。第11组（n=3）仅接受MSC（在第-1、+3、+7、+14、+21天给予）。III组（n=6）接受环孢素A（CsA第0天至+28天）。IV组（n=4）接受预处理照射（第-1天）、BMT（第+1天）和CsA（第0 ~+28天）。第五组（n=5）接受放疗（第-1天）、骨髓移植（第+1天）、CsA（0 ~+28天）和骨髓间充质干细胞（第+1、+7、+14天）。采用流式细胞术和免疫组化法检测CD 4（+）/CD 25（+）T细胞和MSCs的表达和定位。与对照组相比，单独使用MSC的同种异体移植物存活时间显著延长（P=0.02）。CsA处理的同种异体移植物表现出延迟性排斥反应。放射和BMT-CsA治疗显示，与CsA治疗组相比，没有显着的移植物存活益处，但移植物抗宿主病（GVHD）是明显的。联合应用MSCs-BMT-CsA可显著延长移植物存活时间（>200天，P
Background. This Study investigated whether mesenchymal stem cells (MSCs) combined with bone marrow transplantation (BMT), irradiation, or short-term immunosuppressant therapy could prolong composite tissue allotransplant survival in a swine hind-limb model.Methods. Heterotopic hind-limb transplantation was performed in outbred miniature swine. Group I (n=5) was the untreated control. Group 11 (n=3) received MSCs alone (given on days -1, +3, +7, + 14, +21). Group III (n=6) received cyclosporine A (CsA days 0 to +28). Group IV (n=4) received preconditioning irradiation (day - 1), BMT (day + 1), and CsA (days 0 to +28). Group V (n=5) received irradiation (day - 1), BMT (day + 1), CsA (days 0 to +28), and MSCs (days + 1, +7,+ 14). The expression and localization of CD4(+)/CD25(+) T cells and MSCs were assessed using flow cytometry and immunohistochemistry.Results. The allografts survival with MSCs alone revealed a significant prolongation, when compared with the controls (P=0.02). Allografts with CsA treatment exhibited delayed rejection. Irradiation and BMT-CsA treatment revealed no significant allograft survival benefit when compared with the CsA treatment group, but graft-versus-host disease (GVHD) was evident. However, combination of MSCs-BMT-CsA treatment demonstrated significant prolongation of allograft survival (>200 days, P