Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P.R. China.
Research Institute of Nephrology, Zhengzhou University, Zhengzhou, 450052, P.R. China.
Cell Death Dis. 2020 Nov 21;11(11):1000. doi: 10.1038/s41419-020-03206-1.
Diabetic nephropathy, with high prevalence, is the main cause of renal failure in diabetic patients. The strategies for treating DN are limited with not only high cost but an unsatisfied effect. Therefore, the effective treatment of DN needs to be explored urgently. In recent years, due to their self-renewal ability and multi-directional differentiation potential, stem cells have exerted therapeutic effects in many diseases, such as graft-versus-host disease, autoimmune diseases, pancreatic diseases, and even acute kidney injury. With the development of stem cell technology, stem cell-based regenerative medicine has been tried to be applied to the treatment of DN. Related stem cells include embryonic stem cells, induced pluripotent stem cells, mesenchymal cells, and endothelial progenitor cells. Undoubtedly, stem cell transplantation has achieved certain results in the treatment of DN animal models. However, stem cell therapy still remains certain thorny issues during treatment. For instance, poor engraftment and limited differentiation of stem cells caused by the diabetic microenvironment, differentiation into unwanted cell lineages, and malignant transformation or genetic aberrations of stem cells. At present, various researches on the therapeutic effects of stem cells in DN with different opinions are reported and the specific mechanism of stem cells is still unclear. We review here the potential mechanism of stem cells as new therapeutic agents in the treatment of DN. Also, we review recent findings and updated information about not only the utilization of stem cells on DN in both preclinical and clinical trials but limitations and future expectations of stem cell-based therapy for DN.
糖尿病肾病(DN)患病率高,是糖尿病患者肾衰竭的主要原因。DN 的治疗策略不仅费用高,而且效果不理想。因此,迫切需要探索有效的 DN 治疗方法。近年来,由于干细胞具有自我更新能力和多向分化潜能,在移植物抗宿主病、自身免疫性疾病、胰腺疾病甚至急性肾损伤等多种疾病中发挥了治疗作用。随着干细胞技术的发展,基于干细胞的再生医学已尝试应用于 DN 的治疗。相关的干细胞包括胚胎干细胞、诱导多能干细胞、间充质细胞和内皮祖细胞。毫无疑问,干细胞移植在治疗 DN 动物模型方面已经取得了一定的成果。然而,在治疗过程中,干细胞疗法仍然存在一些棘手的问题。例如,由于糖尿病微环境导致干细胞的植入和分化不良、分化为不需要的细胞谱系,以及干细胞的恶性转化或遗传异常。目前,有报道称,不同观点的干细胞在 DN 中的治疗效果的各种研究,并对干细胞的具体机制仍不清楚。我们在这里综述了干细胞作为治疗 DN 的新型治疗剂的潜在机制。此外,我们还回顾了最近的发现和更新的信息,不仅包括临床前和临床试验中干细胞在 DN 中的应用,还包括基于干细胞的治疗 DN 的局限性和未来期望。