Department of Nephrology and Hypertension, Hannover Medical School, 30625 Hannover, Germany.
Biochemistry and Tumor Biology Lab, Department of Gynecology and Obstetrics, Hannover Medical School, 30625 Hannover, Germany.
Int J Mol Sci. 2021 Dec 17;22(24):13562. doi: 10.3390/ijms222413562.
Cellular senescence of renal tubular cells is associated with chronic diseases and age-related kidney disorders. Therapies to antagonize senescence are, therefore, explored as novel approaches in nephropathy. Exosomes derived from human mesenchymal stroma-/stem-like cells (MSC) entail the transfer of multiple bioactive molecules, exhibiting profound regenerative potential in various tissues, including therapeutic effects in kidney diseases. Here, we first demonstrate that exosomes promote proliferation and reduce senescence in aged MSC cultures. For potential therapeutic perspectives in organ rejuvenation, we used MSC-derived exosomes to antagonize senescence in murine kidney primary tubular epithelial cells (PTEC). Exosome treatment efficiently reduced senescence while diminishing the transcription of senescence markers and senescence-associated secretory phenotype (SASP) factors. Concomitantly, we observed less DNA damage foci and more proliferating cells. These data provide new information regarding the therapeutic property of MSC exosomes in the development of renal senescence, suggesting a contribution to a new chapter of regenerative vehicles in senotherapy.
肾小管细胞的衰老与慢性疾病和与年龄相关的肾脏疾病有关。因此，人们探索了拮抗衰老的疗法，将其作为肾病的一种新方法。源自人间质/干细胞样细胞 (MSC) 的外泌体包含多种生物活性分子，在包括肾脏疾病在内的多种组织中表现出很强的再生潜力，具有治疗效果。在这里，我们首先证明外泌体促进衰老 MSC 培养物的增殖和减少衰老。为了在器官年轻化方面的潜在治疗观点，我们使用 MSC 衍生的外泌体来拮抗小鼠肾脏原代肾小管上皮细胞 (PTEC) 的衰老。外体处理有效减少了衰老，同时减少了衰老标志物和衰老相关分泌表型 (SASP) 因子的转录。同时，我们观察到更少的 DNA 损伤焦点和更多的增殖细胞。这些数据提供了关于 MSC 外泌体在肾脏衰老发展中治疗特性的新信息，提示它们有助于衰老治疗中的再生载体的新篇章。
