骨髓干细胞/前体细胞动员促进生长缺血再灌注损伤的修复

背景
了解肾脏损伤的修复和再生机制非常有意义，因为目前没有促进肾脏再生的治疗手段，而且肾脏通常不能完全修复。我们在小鼠的缺血再灌注损伤模型上研究了CD34(+)的骨髓干细胞促进肾脏修复和再生的能力，特别注重于微血管方面。

方法和结果
在肾脏损伤24小时后全身使用人骨髓干细胞，它们选择性地募集到免疫缺陷小鼠(Jackson Labs, Bar Harbor, Me)的受损肾脏，主要聚集在肾脏微血管周围。这种募集与肾脏微血管和肾脏上皮细胞修复、肾功能的改善以及延长小鼠生存时间相关。募集到肾脏的骨髓干细胞表达与循环中内皮细胞的前体细胞同样的标志物，并且合成高水平的促进血管形成的细胞因子，从而导致促进内皮细胞和上皮细胞的增生。

尽管纯化的骨髓干细胞一旦募集到肾脏就可以获得内皮前体细胞的标志物，但是人内皮细胞能植入到小鼠毛细血管壁上非常罕见，提示人干细胞通过旁分泌机制而非替换微血管来介导肾脏修复。

结论
这些研究将骨髓干细胞作为在肾损伤后一种很有希望的治疗手段又向前推进了一步。


Circultion 2010 May 10.

Mobilized Human Hematopoietic Stem/Progenitor Cells Promote Kidney Repair After Ischemia/Reperfusion Injury.
Li B, Cohen A, Hudson TE, Motlagh D, Amrani DL, Duffield JS.
Laboratory of Inflammation Research, Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.

Abstract
BACKGROUND: -Understanding the mechanisms of repair and regeneration of the kidney after injury is of great interest because there are currently no therapies that promote repair, and kidneys frequently do not repair adequately. We studied the capacity of human CD34(+) hematopoietic stem/progenitor cells (HSPCs) to promote kidney repair and regeneration using an established ischemia/reperfusion injury model in mice, with particular focus on the microvasculature.

Methods and Results-Human HSPCs administered systemically 24 hours after kidney injury were selectively recruited to injured kidneys of immunodeficient mice (Jackson Labs, Bar Harbor, Me) and localized prominently in and around vasculature. This recruitment was associated with enhanced repair of the kidney microvasculature, tubule epithelial cells, enhanced functional recovery, and increased survival. HSPCs recruited to kidney expressed markers consistent with circulating endothelial progenitors and synthesized high levels of proangiogenic cytokines, which promoted proliferation of both endothelial and epithelial cells.

Although purified HSPCs acquired endothelial progenitor markers once recruited to the kidney, engraftment of human endothelial cells in the mouse capillary walls was an extremely rare event, indicating that human stem cell mediated renal repair is by paracrine mechanisms rather than replacement of vasculature.

Conclusions-These studies advance human HSPCs as a promising therapeutic strategy for promoting renal repair after injury.

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