Li Xueting, Chen Mingkai, Cao Jinghe, Chen Xinke, Song Hui, Shi Shuo, He Baoyu, Zhang Bin, Zhang Ziteng
Department of Nephrology, Affiliated Hospital of Jining Medical University, Jining, Shandong, PR China.
Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, PR China.
Heliyon. 2024 Aug 28;10(17):e37002. doi: 10.1016/j.heliyon.2024.e37002. eCollection 2024 Sep 15.
Exosomes, which are small nanoscale vesicles capable of secretion, have garnered significant attention in recent years because of their therapeutic potential, particularly in the context of kidney diseases. Notably, human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exos) are emerging as promising targeted therapies for renal conditions. The aim of this study was to investigate the therapeutic effects of hucMSC-Exos on diabetic kidney disease (DKD) both in vivo and in vitro. Additionally, this study seeks to elucidate cellular and molecular differentials, as well as the expression of relevant signaling pathways, through single-cell RNA sequencing. This endeavor was designed to enhance our understanding of the connection between hucMSC-Exos and the pathogenesis of DKD.
The study commenced with the extraction and characterization of hucMSC-Exos, including the determination of their concentrations. Animal experiments were conducted to evaluate the therapeutic potential of hucMSC-Exos in a DKD mouse model. Subsequently, single-cell sequencing was employed to investigate the molecular mechanisms underlying the efficacy of extracellular vesicles in ameliorating DKD. These findings were further substantiated by cell-based experiments. Importantly, the results indicate that hucMSC-Exos can impede the progression of DKD in mice, with macrophage activation playing a pivotal role in this process.
The in vivo experiments conclusively established hucMSC-Exos as a pivotal component in preserving renal function and retarding the progression of DKD. Our utilization of single-cell sequencing technology, in conjunction with in vivo and in vitro experiments, provides compelling evidence that M2 macrophages are instrumental in enhancing the amelioration of diabetic nephropathy.
外泌体是一种能够分泌的纳米级小囊泡，近年来因其治疗潜力，特别是在肾脏疾病方面，而备受关注。值得注意的是，人脐带间充质干细胞衍生的外泌体（hucMSC-Exos）正成为治疗肾脏疾病的有前景的靶向疗法。本研究的目的是在体内和体外研究hucMSC-Exos对糖尿病肾病（DKD）的治疗作用。此外，本研究旨在通过单细胞RNA测序阐明细胞和分子差异以及相关信号通路的表达。这一努力旨在加深我们对hucMSC-Exos与DKD发病机制之间联系的理解。
该研究首先对外泌体进行提取和表征，包括测定其浓度。进行动物实验以评估hucMSC-Exos在DKD小鼠模型中的治疗潜力。随后，采用单细胞测序来研究细胞外囊泡改善DKD疗效的分子机制。这些发现通过基于细胞的实验得到进一步证实。重要的是，结果表明hucMSC-Exos可以阻碍小鼠DKD的进展，巨噬细胞激活在这一过程中起关键作用。
体内实验最终确定hucMSC-Exos是保护肾功能和延缓DKD进展的关键因素。我们利用单细胞测序技术，结合体内和体外实验，提供了令人信服的证据，即M2巨噬细胞有助于增强糖尿病肾病的改善。
