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细胞存活率低限制了间充质干细胞移植对急性肾损伤的有益影响。

Poor cell survival limits the beneficial impact of mesenchymal stem cell transplantation on acute kidney injury.

机构信息

Renal Division, Department of Medicine, University of Cologne, Cologne, Germany.

出版信息

Nephron Exp Nephrol. 2010;114(3):e107-16. doi: 10.1159/000262318. Epub 2009 Dec 2.

Abstract

BACKGROUND

Although renal tubular epithelium has a great capacity for repair it has been suggested that the administration of mesenchymal stem cells may accelerate the recovery following severe ischemic injury.

METHODS

Here we analyzed the survival rate and organ distribution of transplanted mesenchymal stem cells as well as their contribution to kidney regeneration after ischemic renal injury using functional tests, histological examination as well as quantitative real-time PCR.

RESULTS

Intravenously injected stem cells were mainly trapped in lungs and liver. One hour after injection, less than 1% of the injected stem cells could be detected in the injured kidneys. These cells disappeared within the first few days and did not replace renal epithelial cells precluding substantial transdifferentiation. To clarify whether reinforced stem cell delivery might promote sustained survival or conversion to tubular epithelia, stem cells were directly injected into the injured kidneys. Although these grafted cells also did not show sustained survival or contribute to structural renal repair, stem cell injection was associated with a significant but transient initial decrease in serum creatinine.

CONCLUSION

These data suggest that mesenchymal stem cells do not significantly contribute to epithelial renewal after ischemic injury, promoting the idea that the major impact of cell-based therapy for acute kidney injury may result from paracrine or endocrine effects unrelated to stem cell transdifferentiation.

摘要

背景

尽管肾小管上皮细胞具有很强的修复能力,但有研究表明,间充质干细胞的给药可能会加速严重缺血性损伤后的恢复。

方法

在这里,我们使用功能测试、组织学检查和定量实时 PCR 分析了移植间充质干细胞的存活率和器官分布,以及它们对缺血性肾损伤后肾脏再生的贡献。

结果

静脉注射的干细胞主要被捕获在肺部和肝脏中。注射后 1 小时,在受损肾脏中只能检测到不到 1%的注射干细胞。这些细胞在最初几天内消失,并没有取代肾上皮细胞,排除了实质性的转分化。为了阐明增强干细胞输送是否可能促进持续存活或转化为管状上皮细胞,我们直接将干细胞注射到受损的肾脏中。尽管这些移植的细胞也没有显示出持续的存活或有助于结构上的肾脏修复,但干细胞注射与血清肌酐的显著但短暂的初始下降有关。

结论

这些数据表明,间充质干细胞在缺血性损伤后对上皮细胞的更新没有显著贡献,这一观点促进了这样一种想法,即细胞治疗急性肾损伤的主要影响可能来自与干细胞转分化无关的旁分泌或内分泌效应。

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