Departments of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Healthcare Services Management, Nihon University School of Medicine, Tokyo, Japan.
Adv Exp Med Biol. 2018;1103:199-218. doi: 10.1007/978-4-431-56847-6_11.
The kidney plays an essential role in the maintenance of homeostasis in healthy individuals, e.g., by regulating the amount of water and concentration of electrolyte in the body. Owing to the structural complexity, renal dysfunction is caused by a myriad of diseases and conditions, and in severe cases, it progresses to end-stage renal disease in which patients require renal replacement therapy, i.e., maintenance dialysis or kidney transplantation. The currently available therapeutic modalities, with the exception of renal transplantation, cannot recover severely deteriorated renal function. Thus, regenerative medicine holds considerable promise as a potential means for developing next-generation renal therapeutics. Mesenchymal stem cell (MSC) transplantation has been investigated in acute kidney injury and chronic kidney disease models, and clinical studies have already been started for some kinds of kidney diseases. However, most of these studies concluded that the main underlying mechanism of therapeutic effect of MSC transplantation was paracrine. Recently, we reported that Muse cell therapy in a murine model of chronic kidney disease resulted in differentiation of intravenously injected Muse cells into glomerular cells after preferential homing to damaged glomerulus and improvement in renal function. The result suggested the potentiality of Muse cell therapy for glomerular regeneration. Muse cells are a promising cell source for regenerative therapy for kidney diseases.
肾脏在维持健康个体的体内平衡方面起着至关重要的作用,例如,通过调节体内水的含量和电解质的浓度。由于结构复杂,肾功能障碍是由多种疾病和情况引起的,在严重的情况下,它会进展为终末期肾病,患者需要肾脏替代治疗,即维持透析或肾移植。目前可用的治疗方法,除了肾移植,都不能恢复严重受损的肾功能。因此,再生医学作为开发下一代肾脏治疗方法的一种有前途的手段具有相当大的潜力。间充质干细胞(MSC)移植已在急性肾损伤和慢性肾病模型中进行了研究,并且已经开始对某些类型的肾病进行临床研究。然而,这些研究大多得出结论,MSC 移植治疗效果的主要潜在机制是旁分泌。最近,我们报告称,在慢性肾病的小鼠模型中进行 Muse 细胞治疗后,静脉注射的 Muse 细胞优先归巢到受损的肾小球,并改善肾功能,导致 Muse 细胞分化为肾小球细胞。这一结果表明 Muse 细胞治疗具有肾小球再生的潜力。Muse 细胞是肾脏疾病再生治疗的一种有前途的细胞来源。