Poor Cell Survival Limits the Beneficial Impact of Mesenchymal Stem Cell Transplantation on Acute Kidney Injury
Poor Cell Survival Limits the Beneficial Impact of Mesenchymal Stem Cell Transplantation on Acute Kidney Injury
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DOI：
10.1159/000262318
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发表时间：
2010-01-01
影响因子：
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通讯作者：
Benzing, Thomas
中科院分区：
文献类型：
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作者：
Burst, Volker R.;Gillis, Meyke;Benzing, Thomas
背景资料：虽然肾小管上皮细胞具有很强的修复能力，但已经提出给予间充质干细胞可以加速严重缺血性损伤后的恢复。研究方法：在这里，我们分析了移植的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的肾脏再生的贡献，使用功能测试，组织学检查以及定量实时PCR。结果：腹腔注射的干细胞主要滞留在肺和肝内。注射后一小时，在受损的肾脏中检测到不到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，排除了大量的转分化。为了阐明强化的干细胞递送是否可能促进持续的存活或转化为肾小管上皮细胞，将干细胞直接注射到受损的肾脏中。尽管这些移植细胞也没有表现出持续的存活或有助于结构性肾修复，但干细胞注射与血清肌酐的显著但短暂的初始降低相关。结论：这些数据表明，间充质干细胞并没有显着促进缺血性损伤后上皮更新，促进急性肾损伤的细胞为基础的治疗的主要影响的想法，可能会导致旁分泌或内分泌作用无关的干细胞转分化。版权所有（C）2009 S. Karger AG，巴塞尔
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. Copyright (C) 2009 S. Karger AG, Basel