Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Stem Cells. 2010 Mar 31;28(3):513-22. doi: 10.1002/stem.293.
In search for new sources of mesenchymal stem cells (MSCs) for renal repair in acute kidney injury (AKI), we investigated the potential of human cord blood (CB)-MSCs to cure mice with AKI. Infusion of CB-MSCs in immunodeficient mice with cisplatin-induced AKI ameliorated both renal function and tubular cell injury, and prolonged survival. Transplanted CB-MSCs localized in peritubular areas, limited capillary alterations and neutrophil infiltration. Apoptosis reduced and tubular cell proliferation increased by virtue of stem cell capacity to produce growth factors. The reno-protective effect of CB-MSCs was further confirmed by their ability to inhibit oxidative damage and to induce the prosurvival factor Akt in tubular cells. The evidence that CB-MSCs in vitro increased the production of growth factors and inhibited IL-1 beta and TNFalpha synthesis when cocultured with damaged proximal tubular cells indicates a regenerative and anti-inflammatory action of stem cell treatment. Altogether these results highlight the potential of human CB-MSCs as future cell therapy for testing in human AKI.
为了寻找新的间充质干细胞（MSCs）来源以用于急性肾损伤（AKI）的肾脏修复，我们研究了人脐血（CB）-MSCs 治疗 AKI 小鼠的潜力。在顺铂诱导的 AKI 免疫缺陷小鼠中输注 CB-MSCs 可改善肾功能和肾小管细胞损伤，并延长其生存时间。移植的 CB-MSCs 定位于肾小管周围区域，可限制毛细血管改变和中性粒细胞浸润。通过干细胞产生生长因子的能力，减少了细胞凋亡并增加了肾小管细胞的增殖。CB-MSCs 抑制氧化损伤和诱导肾小管细胞中存活因子 Akt 的能力进一步证实了其肾保护作用。体外实验结果表明，CB-MSCs 与受损的近端肾小管细胞共培养时可增加生长因子的产生并抑制 IL-1β和 TNFα的合成，这表明干细胞治疗具有再生和抗炎作用。总之，这些结果突出了人 CB-MSCs 作为未来细胞治疗在人类 AKI 中的应用潜力。
