Mesenchymal stem cells home to injured tissues when co-infused with hematopoietic cells to treat a radiation-induced multi-organ failure syndrome
Mesenchymal stem cells home to injured tissues when co-infused with hematopoietic cells to treat a radiation-induced multi-organ failure syndrome
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DOI：
10.1002/jgm.452
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发表时间：
2003-12-01
影响因子：
3.5
通讯作者：
Thierry, D
中科院分区：
文献类型：
--
作者：
Chapel, A;Bertho, JM;Thierry, D
背景：最近的研究表明，自体造血细胞的体外扩增可能是治疗骨髓衰竭的一种选择。我们研究了联合输注自体离体扩增的造血细胞与间充质干细胞（MSC）治疗多器官衰竭综合征后照射在非人灵长类动物model.Methods造血细胞和MSC从骨髓抽吸物扩大的潜力。用编码绿色荧光蛋白（e-GFP）的基因转导MSC，以便在输注后追踪它们。研究了12只动物。9只动物接受来自中子/伽马源的8戈伊全身照射，从而导致非均匀暴露; 3只动物接受假照射。用扩增的造血干细胞和MSC、单独的扩增的造血干细胞或单独的MSC处理动物。未经处理的骨髓细胞移植作为controls.Results依赖于中子/伽马比，不同的严重程度，但性质相似的急性放射病的结果。GFP标记的细胞被发现在受伤的肌肉，皮肤，骨髓和肠道的治疗动物通过PCR高达82 days postinfus.Conclusions这是第一个证据的扩增的MSC归巢在许多组织后，严重的多器官损伤的灵长类动物。转导的MSC的定位与辐射的严重程度和几何形状相关。在各种组织中观察到修复过程。间充质干细胞的可塑性潜力及其对体内修复过程的贡献仍有待研究。版权所有（C）2003约翰威利父子有限公司。
Background Recent studies have suggested that ex vivo expansion of autologous hematopoietic cells could be a therapy of choice for the treatment of bone marrow failure. We investigated the potential of a combined infusion of autologous ex vivo expanded hematopoietic cells with mesenchymal (MSCs) for the treatment of multiorgan failure syndrome following irradiation in a non-human primate model.Methods Hematopoietic cells and MSCs were expanded from bone marrow aspirates. MSCs were transduced with the gene encoding for the green fluorescent protein (e-GFP), in order to track them following infusion. Twelve animals were studied. Nine animals received total-body irradiation at 8 Gy from a neutron/gamma source thus resulting in heterogeneous exposure; three animals were sham-irradiated. The animals were treated with expanded hematopoietic stem cells and MSCs, expanded hematopoietic stem cells alone, or MSCs alone. Unmanipulated bone marrow cell transplants were used as controls.Results Depending on the neutron/gamma ratio, an acute radiation sickness of varying severity but of similar nature resulted. GFP-labeled cells were found in the injured muscle, skin, bone marrow and gut of the treated animals via PCR up to 82 days post-infusion.Conclusions This is the first evidence of expanded MSCs homing in numerous tissues following a severe multi-organ injury in primates. Localization of the transduced MSCs correlated to the severity and geometry of irradiation. A repair process was observed in various tissues. The plasticity potential of the MSCs and their contribution to the repair process in vivo remains to be studied. Copyright (C) 2003 John Wiley Sons, Ltd.