Humphreys Benjamin D, Bonventre Joseph V
Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Annu Rev Med. 2008;59:311-25. doi: 10.1146/annurev.med.59.061506.154239.
The potential role of mesenchymal stem cells (MSCs, also called mesenchymal stromal cells) in endogenous repair and cell-based therapies for acute kidney injury (AKI) is under intensive investigation. Preclinical studies indicate that administered MSCs both ameliorate renal injury and accelerate repair. These versatile cells home to sites of injury, where they modulate the repair process. The mechanisms responsible for their protective and regenerative effects are incompletely understood. Some have reported that MSCs are capable of direct engraftment into injured nephrons under certain circumstances. This is highly controversial, however, and even those who argue there is engraftment acknowledge that the primary means of repair by these cells most likely involves paracrine and endocrine effects, including mitogenic, antiapoptotic, anti-inflammatory, and angiogenic influences. There is a good deal of interest in MSC-based approaches for the treatment of human kidney injury, thanks to positive preclinical results, the strong clinical need for novel therapies to treat AKI, the ease of isolation and expansion of MSCs, and encouraging preliminary clinical trial results in other fields. This review summarizes current knowledge and identifies gaps in our understanding of MSC biology that will need to be filled in order to translate recent discoveries into therapies for AKI in humans.
间充质干细胞(MSCs,也称为间充质基质细胞)在急性肾损伤(AKI)的内源性修复和基于细胞的治疗中的潜在作用正在深入研究中。临床前研究表明,给予的MSCs既能改善肾损伤又能加速修复。这些多功能细胞归巢至损伤部位,在那里它们调节修复过程。其保护和再生作用的机制尚未完全了解。一些人报告说,在某些情况下,MSCs能够直接植入受损的肾单位。然而,这极具争议性,甚至那些认为存在植入的人也承认,这些细胞的主要修复方式很可能涉及旁分泌和内分泌作用,包括促有丝分裂、抗凋亡、抗炎和血管生成影响。由于临床前的积极结果、治疗AKI的新疗法的强烈临床需求、MSCs易于分离和扩增以及在其他领域令人鼓舞的初步临床试验结果,基于MSCs的治疗人类肾损伤的方法引起了广泛关注。本综述总结了当前的知识,并确定了我们对MSCs生物学理解中的差距,为了将最近的发现转化为人类AKI的治疗方法,这些差距需要填补。