Chhabra Preeti, Brayman Kenneth L
Department of Surgery, University of Virginia, Health Sciences Center, Charlottesville, Virginia 22908, USA.
Curr Opin Organ Transplant. 2009 Feb;14(1):72-8. doi: 10.1097/MOT.0b013e328320d2f5.
Acute and chronic kidney disease is a leading cause of morbidity and mortality worldwide with overall mortality rates between 50 and 80%. An acute shortage of compatible organs coupled with limited adaptability of current dialysis techniques has created a sense of urgency to investigate new alternatives, and the purpose of this review is to provide a concise overview of current stem cell-based strategies in renal repair following acute kidney injury.
Bone marrow-derived mesenchymal stem cells hold therapeutic potential in repairing tubular injury, ameliorating renal function deficits, and prolonging survival in experimental models of acute kidney injury. These renoprotective effects are mediated mainly by paracrine mechanisms that act on surviving tubular cells by stimulating dedifferentiation, proliferation, migration, and eventually redifferentiation into mature epithelial cells as well as by stimulating expansion and differentiation of resident stem/progenitor cells. Mesenchymal stem cells are capable of immunosuppression as well as inducing protection against peritubular capillary changes following acute injury making them ideal for allogeneic cell therapy.
Autologous transplantation of bone marrow-derived mesenchymal stem cells as well as adult renal stem/progenitor cells that can be easily harvested and expanded may be the solution to limited donor organ availability and chronic immunosuppressive therapy.
急性和慢性肾脏病是全球发病和死亡的主要原因,总体死亡率在50%至80%之间。可兼容器官的严重短缺以及当前透析技术有限的适应性催生了研究新替代方案的紧迫感,本综述旨在简要概述目前急性肾损伤后基于干细胞的肾脏修复策略。
在急性肾损伤的实验模型中,骨髓间充质干细胞在修复肾小管损伤、改善肾功能缺陷以及延长生存期方面具有治疗潜力。这些肾脏保护作用主要通过旁分泌机制介导,该机制作用于存活的肾小管细胞,刺激其去分化、增殖、迁移,并最终再分化为成熟上皮细胞,同时刺激驻留干细胞/祖细胞的扩增和分化。间充质干细胞具有免疫抑制作用,还能诱导对急性损伤后肾小管周围毛细血管变化的保护作用,使其成为同种异体细胞治疗的理想选择。
自体移植易于获取和扩增的骨髓间充质干细胞以及成体肾干细胞/祖细胞,可能是解决供体器官可用性有限和慢性免疫抑制治疗问题的方法。