Herrera Maria Beatriz, Bussolati Benedetta, Bruno Stefania, Fonsato Valentina, Romanazzi Giuseppe Mauriello, Camussi Giovanni
Cattedra di Nefrologia, Dipartimento di Medicina Interna, Università di Torino, and Centro Ricerca Medicina Sperimentale, 10126 Torino, Italy.
Int J Mol Med. 2004 Dec;14(6):1035-41.
Acute renal failure (ARF) is a common disease with high morbidity and mortality. Recovery from ARF is dependent on the replacement of necrotic tubular cells with functional tubular epithelium. Recent advancement in developmental biology led to the discovery of immature mesenchymal stem cells (MSCs) in bone marrow and several established organs and to the definition of their potential in the recovery from tissue injury. We investigated the effect of MSCs infusion on the recovery from ARF induced by intramuscle injection of glycerol in C57/BL6 mice. In this model, ARF is associated with an extensive necrosis of tubular epithelial cells due to myoglobin- and hemoglobin-induced injury. MSCs were obtained from bone marrow of transgenic mice expressing green fluorescent protein (GFP). MSC GFP-positive cells (MSC-GFP(+)) injected intravenously homed to the kidney of mice with glycerol-induced ARF but not to the kidney of normal mice. MSC-GFP(+) localized in the context of the tubular epithelial lining and expressed cytokeratin, indicating that MSCs engrafted in the damaged kidney, differentiated into tubular epithelial cells and promoted the recovery of morphological and functional alterations. Moreover, MSCs enhanced tubular proliferation as detected by the increased number of proliferating cell nuclear antigen (PCNA) positive cells. A significant contribution of the engrafted MSCs in the regeneration of tubular epithelial cells was shown by the presence of a consistent number of GFP(+) tubular cells 21 days after the induction of injury. In conclusion, these results indicated a tropism of MSCs for the injured kidney and a potential contribution of these cells to tubular regeneration and to the recovery from ARF.
急性肾衰竭（ARF）是一种发病率和死亡率都很高的常见疾病。ARF的恢复取决于用功能性肾小管上皮细胞替代坏死的肾小管细胞。发育生物学的最新进展导致在骨髓和几个成熟器官中发现了未成熟的间充质干细胞（MSCs），并明确了它们在组织损伤恢复中的潜力。我们研究了在C57/BL6小鼠中，静脉输注MSCs对肌肉注射甘油诱导的ARF恢复的影响。在这个模型中，ARF与肌红蛋白和血红蛋白诱导的损伤导致的肾小管上皮细胞广泛坏死有关。MSCs取自表达绿色荧光蛋白（GFP）的转基因小鼠的骨髓。静脉注射的绿色荧光蛋白阳性的MSCs（MSC-GFP(+)）归巢到甘油诱导的ARF小鼠的肾脏，但不归巢到正常小鼠的肾脏。MSC-GFP(+)定位于肾小管上皮内衬，表达细胞角蛋白，表明MSCs植入受损肾脏，分化为肾小管上皮细胞，并促进形态和功能改变的恢复。此外，通过增殖细胞核抗原（PCNA）阳性细胞数量增加检测到MSCs增强了肾小管增殖。损伤诱导21天后，一致数量的GFP(+)肾小管细胞的存在表明植入的MSCs对肾小管上皮细胞再生有显著贡献。总之，这些结果表明MSCs对受损肾脏具有趋向性，并且这些细胞对肾小管再生和ARF恢复有潜在贡献。
