Imberti Barbara, Morigi Marina, Benigni Ariela
'Mario Negri' Institute for Pharmacological Research, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso , Bergamo, Italy.
Kidney Int Suppl (2011). 2011 Sep;1(3):90-93. doi: 10.1038/kisup.2011.21.
Current interventions for the treatment of acute kidney injury (AKI) are not satisfactory, and it is time to approach new strategies in order to definitely take a step forward. At its beginning, cell therapy was innovative and promising. We have shown that mesenchymal stem cells (MSCs), isolated from human and murine bone marrow (BM), behave as an efficacious tool for the treatment of cisplatin-induced AKI in mice in terms of amelioration of renal function and structure, and animal survival. Although the mechanism has not been completely elucidated, we have provided data showing that BM-MSC-mediated renal recovery involves the release at the site of injury of the growth factor, insulin-like growth factor-1. Several biological effects have been observed in renal tissues of mice treated with BM-MSCs, including increased cell proliferation, hemodynamic changes, and cell apoptosis reduction. In the same experimental model, we have tested the effect of MSCs isolated from cord blood (CB-MSCs), which, similar to BM-MSCs, not only ameliorated renal function but also protected animals from death to a remarkably higher extent. Animals receiving CB-MSCs showed reduction of oxidative stress and activation of AKT prosurvival pathway in tubular cells. These results hold great promise for future studies in patients with AKI.
目前用于治疗急性肾损伤(AKI)的干预措施并不令人满意,现在是时候采用新策略以便切实向前迈出一步了。起初,细胞疗法具有创新性且前景广阔。我们已经表明,从人和小鼠骨髓(BM)中分离出的间充质干细胞(MSCs),在改善肾功能和结构以及提高动物存活率方面,是治疗小鼠顺铂诱导的急性肾损伤的有效工具。尽管其机制尚未完全阐明,但我们已提供数据表明,骨髓间充质干细胞介导的肾脏恢复涉及在损伤部位释放生长因子胰岛素样生长因子-1。在用骨髓间充质干细胞治疗的小鼠肾组织中观察到了几种生物学效应,包括细胞增殖增加、血流动力学变化以及细胞凋亡减少。在同一实验模型中,我们测试了从脐带血中分离出的间充质干细胞(CB-MSCs)的效果,与骨髓间充质干细胞类似,它们不仅改善了肾功能,而且在更高程度上保护动物免于死亡。接受脐带血间充质干细胞的动物表现出氧化应激减轻以及肾小管细胞中AKT促生存途径的激活。这些结果为未来对急性肾损伤患者的研究带来了巨大希望。