Haematopoietic lineage-committed bone marrow cells, but not cloned cultured mesenchymal stem cells, contribute to regeneration of renal tubular epithelium after HgCl2-induced acute tubular injury
Haematopoietic lineage-committed bone marrow cells, but not cloned cultured mesenchymal stem cells, contribute to regeneration of renal tubular epithelium after HgCl2-induced acute tubular injury
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DOI：
10.1111/j.1365-2184.2008.00545.x
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发表时间：
2008-08-01
影响因子：
8.5
通讯作者：
Poulsom, R.
中科院分区：
文献类型：
--
作者：
Fang, T. -C.;Otto, W. R.;Poulsom, R.
目的：我们以前的研究表明，内源性骨髓细胞（BMCs）有助于急性肾小管损伤后的肾小管再生。本研究的目的是检查哪部分BMCs，造血谱系骨髓细胞（HLMCs）或间充质干细胞（MSCs），是有效的。材料与方法：对6周龄雌性小鼠进行致死性照射，并移植雌性增强型绿色荧光蛋白阳性（GFP（+））、可塑性非粘附骨髓细胞（作为HLMCs的来源）加上克隆培养的雄性GFP（-）MSC。四周后，将它们分为两组：对照组小鼠和HgCl治疗组小鼠（2）。在动物处死前1小时给予氚化胸苷，每隔2周进行一次。对肾脏切片进行肾小管上皮标记物染色，通过GFP免疫组织化学或Y染色体原位杂交指示细胞来源;进行过碘酸-希夫染色，并对样品进行放射自显影。将每只小鼠1000个连续的肾小管上皮细胞在S期中评分为雌性（固有的）GFP（+）（HLMC衍生的）或雄性（MSC衍生的）。结果如下：造血谱系骨髓细胞和MSC稳定植入骨髓和脾脏，但只有HLMC衍生的细胞，而不是MSC，被发现在肾小管，并能够进行DNA合成后，急性肾损伤。在肾间质中检测到少量MSC，但其重要性需要进一步探讨。结论：造血系骨髓细胞，而不是克隆培养的MSC，不仅可以在肾小管细胞的正常磨损和撕裂周转中发挥作用，而且还可以在肾小管损伤后的修复中发挥作用。
Objective: Our previous studies have demonstrated that endogenous bone marrow cells (BMCs) contribute to renal tubular regeneration after acute tubular injury. The aim of this study was to examine which fraction of BMCs, haematopoietic lineage marrow cells (HLMCs) or mesenchymal stem cells (MSCs), are effective. Materials and methods: Six-week-old female mice were lethally irradiated and were transplanted with female enhanced green fluorescent protein-positive (GFP(+)), plastic non-adherent marrow cells (as a source of HLMCs) plus cloned cultured male GFP(-) MSCs. Four weeks later, they were assigned into two groups: control mice with vehicle treatment and mice treated with HgCl(2). Tritiated thymidine was given 1 h before animal killing which occurred at intervals over 2 weeks. Kidney sections were stained for a tubular epithelial marker, cell origin indicated by GFP immunohistochemistry or Y chromosome in situ hybridization; periodic acid-Schiff staining was performed, and samples were subjected to autoradiography. One thousand consecutive renal tubular epithelial cells per mouse, in S phase, were scored as either female (indigenous) GFP(+) (HLMC-derived) or male (MSC-derived). Results: Haematopoietic lineage marrow cells and MSCs stably engrafted into bone marrow and spleen, but only HLMC-derived cells, not MSCs, were found in the renal tubules and were able to undergo DNA synthesis after acute renal injury. A few MSCs were detected in the renal interstitium, but their importance needs to be further explored. Conclusion: Haematopoietic lineage marrow cells, but not cloned cultured MSCs, can play a role not only in normal wear-and-tear turnover of renal tubular cells, but also in repair after tubular injury.