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骨髓间充质干细胞对致敏小鼠造血干/祖细胞移植植入的影响

Effect of bone marrow mesenchymal stem cells on engraftment of hematopoietic stem/progenitor cells in sensitized mice
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摘要 目的:前期的研究已经证实致敏小鼠造血干/祖细胞移植植入失败率高。本研究拟通过骨髓间充质干细胞(MSCs)进行干预,观察能否提高造血干、祖细胞移植的植入率。方法:应用贴壁培养法体外培养正常小鼠骨髓MSCs,并分为6个实验组,包括实验组1:d11 MSCs干预的致敏组;实验组2:d0 MSCs干预的致敏组;实验组3:d11和d0 2次MSCs干预的致敏组;实验组4:无MSCs干预的致敏小鼠对照组;实验组5:无MSCs干预的正常小鼠(非致敏小鼠)移植对照组;实验组6:无MSCs干预的正常小鼠不移植对照组。观察指标包括生存分析、移植效果分析(血象改变、骨髓细胞恢复及嵌合分析等)和移植物抗宿主病(GVHD)检测,最终评估MSCs干预对各实验组异基因造血干/祖细胞移植植入率的影响效果。结果:与对照组(实验组4、5、6)比较,MSCs干预(实验组1、2、3)在2次异基因脾细胞注射法致敏的动物模型进行异基因造血干/祖细胞移植时,未能促进骨髓造血干/祖细胞移植的植入,也未能延长致敏动物移植后的生存时间。结论:体内应用1×106MSCs干预,未能促进2次异基因1×106C57BL/6小鼠脾细胞输注法建立的重度致敏模型异基因造血干/祖细胞移植的植入。 AIM: To evaluate the effects of bone marrow-derived mesenchymal stem cells(MSCs) on engraftment of hematopoietic stem/progenitor cells in sensitized mice.METHODS: Mouse bone marrow-derived MSCs were cultured by adherent culture method.MSCs combined with or without hematopoietic stem/progenitor cells were implanted into the sensitized mouse model,which was established by allogeneic splenocyte transfusion,and were divided into 6 groups: MSC intervention groups,including sensitized mice with MSCs on day 11,sensitized mice with MSCs on day 0 and sensitized-mice with MSCs both on day 11 and day 0;control groups,including sensitized mice without MSC intervention,non-sensitized mice without MSC intervention and non-sensitized mice without MSCs or transplantation of hematopoietic stem/progenitor cells.The survivors were assessed after transplantation and hematopoietic recovery was monitored weekly including hematological change,immune function reconstruction,bone marrow cell recovery,chimera analysis and graft-versus-host disease development.RESULTS: Compared with different control groups,MSC intervention did not prolong the survival rates of the sensitized model mice after lethal irradiation.CONCLUSION: Under the experimental conditions,MSC combined with C57BL/6 bone marrow hematopoietic stem/progenitor cells fail to promote the growth of engraftment in C57BL/6 allogeneic splenocyte-sensitized BALB/c mice in vivo.
出处 《中国病理生理杂志》 CAS CSCD 北大核心 2012年第1期124-130,共7页 Chinese Journal of Pathophysiology
基金 国家自然科学基金资金资助项目(No.30872383)
关键词 骨髓间充质干细胞 致敏小鼠 造血干/祖细胞移植 Bone marrow mesenchymal stem cells Sensitized mice Hematopoietic stem/progenitor cell transplantation
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