Transplantation of vascular endothelial cells mediates the hematopoietic recovery and survival of lethally irradiated mice
Transplantation of vascular endothelial cells mediates the hematopoietic recovery and survival of lethally irradiated mice
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DOI：
10.1182/blood-2006-05-022640
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发表时间：
2007-03-15
期刊：
影响因子：
20.3
通讯作者：
Chao, Nelson J.
中科院分区：
文献类型：
--
作者：
Chute, John P.;Muramoto, Garrett G.;Chao, Nelson J.
Flk-1（+）内皮祖细胞对胚胎发生期间造血的确定性开始起关键作用。最近的研究表明，成人来源的内皮细胞也具有造血活性。在这项研究中，我们试图确定移植原代血管内皮细胞（ECs）是否可以提高辐射小鼠的造血恢复和生存。将C57 B16小鼠暴露于亚致死和致死剂量的辐射，随后给予原代鼠脑源性EC（MBEC）或胎血源性EC（FBEC）移植。与对照组相比，接受单独MBEC移植的小鼠表现出加速的BM细胞恢复，BM c-kit（+）sca-1（-）lin（-）祖细胞的辐射保护作用和增强的c-kit（+）sca-1（+）lin（-）（KSL）干/祖细胞再生。MBEC移植还促进了辐射暴露后循环白色血细胞和血小板计数的恢复。值得注意的是，57%接受单独MBEC移植的小鼠在1050 cGy照射后长期存活，这在对照小鼠中是100%致死的。与对照组相比，FBEC移植也与存活率增加相关，尽管这些小鼠不能长期存活。这些数据表明，内皮细胞活性的重建可以改善辐射小鼠的造血恢复和生存。
Flk-1(+) endothelial progenitors contribute critically to the definitive onset of hematopoiesis during embryogenesis. Recent studies have suggested that adult sources of endothelial cells also possess hematopoietic activity. In this study, we sought to determine whether transplantation of primary vascular endothelial cells (ECs) could enhance the hematopoietic recovery and survival of irradiated mice. C57B16 mice were exposed to sublethal and lethal doses of irradiation and were subsequently given transplants of either primary murine brain-derived ECs (MBECs) or fetal blood-derived ECs (FBECs). Mice that received a transplant with MBECs alone demonstrated accelerated BM cellular recovery, radioprotection of BM c-kit(+)sca-1(-)lin(-) progenitors and enhanced regeneration of c-kit(+)sca-l(+)lin(-)(KSL) stem/progenitor cells following irradiation compared with controls. MBEC transplantation also facilitated the recovery of circulating white blood cell and platelet counts following radiation exposure. Remarkably, 57% of mice that received a transplant with MBECs alone survived long term following 1050 cGy exposure, which was 100% lethal in control mice. FBEC transplantation was also associated with increased survival compared with controls, although these mice did not survive in the long term. These data suggest that reestablishment of endothelial cell activity can improve the hematopoietic recovery and survival of irradiated mice.