Diabetic kidney disease (DKD) is a microvascular complication of diabetes mellitus (DM) and comprises multifactorial pathophysiologic mechanisms. Despite current treatment, around 30-40% of individuals with type 1 and type 2 DM (DM1 and DM2) have progressive DKD, which is the most common cause of end-stage chronic kidney disease worldwide. Mesenchymal stem cell- (MSC-) based therapy has important biological and therapeutic implications for curtailing DKD progression. As a chronic disease, DM may impair MSC microenvironment, but there is compelling evidence that MSC derived from DM1 individuals maintain their cardinal properties, such as potency, secretion of trophic factors, and modulation of immune cells, so that both autologous and allogeneic MSCs are safe and effective. Conversely, MSCs derived from DM2 individuals are usually dysfunctional, exhibiting higher rates of senescence and apoptosis and a decrease in clonogenicity, proliferation, and angiogenesis potential. Therefore, more studies in humans are needed to reach a conclusion if autologous MSCs from DM2 individuals are effective for treatment of DM-related complications. Importantly, the bench to bedside pathway has been constructed in the last decade for assessing the therapeutic potential of MSCs in the DM setting. Laboratory research set the basis for establishing further translation research including preclinical development and proof of concept in model systems. Phase I clinical trials have evaluated the safety profile of MSC-based therapy in humans, and phase II clinical trials (proof of concept in trial participants) still need to answer important questions for treating DKD, yet metabolic control has already been documented. Therefore, randomized and controlled trials considering the source, optimal cell number, and route of delivery in DM patients are further required to advance MSC-based therapy. Future directions include strategies to reduce MSC heterogeneity, standardized protocols for isolation and expansion of those cells, and the development of well-designed large-scale trials to show significant efficacy during a long follow-up, mainly in individuals with DKD.

中文翻译：

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间充质干细胞疗法治疗糖尿病性肾脏疾病：使用同系，自体，同种异体和异种细胞的研究综述

糖尿病肾病（DKD）是糖尿病（DM）的微血管并发症，并包括多因素病理生理机制。尽管有目前的治疗方法，但约30-40％的1型和2型DM（DM1和DM2）个体患有进行性DKD，这是全世界终末期慢性肾脏疾病的最常见原因。基于间充质干细胞（MSC-）的治疗对减少DKD进展具有重要的生物学和治疗意义。作为一种慢性疾病，DM可能会损害MSC的微环境，但令人信服的证据表明，源自DM1个体的MSC保持其基本特性，例如效力，营养因子的分泌和免疫细胞的调节，因此自体和同种MSC都是安全有效。相反，源自DM2个体的MSC通常功能异常，表现出更高的衰老和凋亡率以及克隆形成性，增殖和血管生成潜能的降低。因此，如果来自DM2个体的自体MSC能有效治疗DM相关并发症，则需要对人类进行更多研究才能得出结论。重要的是，近十年来已经建立了从长凳到床旁的途径，用于评估DM环境中MSC的治疗潜力。实验室研究为建立进一步的翻译研究（包括临床前开发和模型系统中的概念证明）奠定了基础。一期临床试验已评估了基于MSC的疗法对人体的安全性，而二期临床试验（试验参与者的概念证明）仍需要回答治疗DKD的重要问题，然而，代谢控制已被记录在案。因此，还需要考虑DM患者来源，最佳细胞数量和分娩途径的随机和对照试验，以推进基于MSC的治疗。未来的方向包括减少MSC异质性的策略，用于分离和扩增这些细胞的标准化方案以及开发精心设计的大规模试验，以期在长期随访中显示出显着的疗效，主要是针对DKD患者。