Intravenous transplantation of allogeneic bone marrow mesenchymal stem cells and its directional migration to the necrotic femoral head.

Intravenous transplantation of allogeneic bone marrow mesenchymal stem cells and its directional migration to the necrotic femoral head.
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同种异体骨髓间充质干细胞静脉移植及其向坏死股骨头的定向迁移

DOI:
10.7150/ijms.8.74
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发表时间:
2011-01-09
影响因子:
3.6
通讯作者:
Shao NS
Shao NS
中科院分区:
医学4区
文献类型:
--
作者:
Li ZH;Liao W;Cui XL;Zhao Q;Liu M;Chen YH;Liu TS;Liu NL;Wang F;Yi Y;Shao NS

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本研究探讨了同种异体骨髓间充质干细胞(MSCs)静脉移植用于股骨头修复的可行性和安全性,并观察了MSCs在宿主体内的迁移和分布。在体外用绿色荧光蛋白(GFP)标记MSCs,经尾静脉注射到裸鼠体内,并在移植后0、6、24、48、72和96 h动态监测MSCs的分布。在兔股骨头坏死模型建立2周后,通过耳静脉注射GFP标记的MSCs,观察免疫排斥反应和移植物抗宿主病,并在移植后2、4和6 w采集坏死和正常股骨头、骨髓、肺和肝脏。在荧光显微镜下观察组织切片。超过70%的MSCs在标记后72小时成功地用GFP标记。MSCs均匀分布于裸鼠的脑、肺、心、肾、肠、双侧髋关节等多个脏器组织中。家兔静脉移植后6 w,肺、肝、骨髓及正常和坏死兔股骨头中均可见GFP标记的MSCs,且骨髓中MSCs的数量高于股骨头、肝和肺。此外,MSCs的数量在移植后6 w达到峰值。兔移植后无免疫排斥反应和移植物抗宿主病。结果表明,静脉植入的MSCs能够迁移到宿主股骨头中,特别是在坏死股骨头中定向迁移和存活。因此,同种异体间充质干细胞静脉移植治疗股骨头坏死是可行和安全的。
In this study, we investigated the feasibility and safety of intravenous transplantation of allogeneic bone marrow mesenchymal stem cells (MSCs) for femoral head repair, and observed the migration and distribution of MSCs in hosts. MSCs were labeled with green fluorescent protein (GFP) in vitro and injected into nude mice via vena caudalis, and the distribution of MSCs was dynamically monitored at 0, 6, 24, 48, 72 and 96 h after transplantation. Two weeks after the establishment of a rabbit model of femoral head necrosis, GFP labeled MSCs were injected into these rabbits via ear vein, immunological rejection and graft versus host disease were observed and necrotic and normal femoral heads, bone marrows, lungs, and livers were harvested at 2, 4 and 6 w after transplantation. The sections of these tissues were observed under fluorescent microscope. More than 70 % MSCs were successfully labeled with GFP at 72 h after labeling. MSCs were uniformly distributed in multiple organs and tissues including brain, lungs, heart, kidneys, intestine and bilateral hip joints of nude mice. In rabbits, at 6 w after intravenous transplantation, GFP labeled MSCs were noted in the lungs, liver, bone marrow and normal and necrotic femoral heads of rabbits, and the number of MSCs in bone marrow was higher than that in the, femoral head, liver and lungs. Furthermore, the number of MSCs peaked at 6 w after transplantation. Moreover, no immunological rejection and graft versus host disease were found after transplantation in rabbits. Our results revealed intravenously implanted MSCs could migrate into the femoral head of hosts, and especially migrate directionally and survive in the necrotic femoral heads. Thus, it is feasible and safe to treat femoral head necrosis by intravenous transplantation of allogeneic MSCs.
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