Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
Urology Department, Urology Research Institute, Organ Transplantation Center, West China Hospital, Sichuan University, Sichuan, China.
Am J Physiol Renal Physiol. 2022 Nov 1;323(5):F527-F538. doi: 10.1152/ajprenal.00064.2022. Epub 2022 Sep 1.
Pericytes are considered reparative mesenchymal stem cell-like cells, but their ability to ameliorate chronic ischemic kidney injury is unknown. We hypothesized that pericytes would exhibit renoprotective effects in murine renal artery stenosis (RAS). Porcine kidney-derived pericytes (5 × 10) or vehicle were injected into the carotid artery 2 wk after the induction of unilateral RAS in mice. The stenotic kidney glomerular filtration rate and tissue oxygenation were measured 2 wk later using magnetic resonance imaging. We subsequently compared kidney oxidative stress, inflammation, apoptosis, fibrosis, and systemic levels of oxidative and inflammatory cytokines. Treatment of xenogeneic pericytes ameliorated the RAS-induced loss of perfusion, glomerular filtration rate, and atrophy in stenotic kidneys and restored cortical and medullary oxygenation but did not blunt hypertension. Ex vivo, pericytes injection partially mitigated RAS-induced renal inflammation, fibrosis, oxidative stress, apoptosis, and senescence. Furthermore, coculture with pericytes in vitro protected pig kidney-1 tubular cells from injury. In conclusion, exogenous delivery of renal pericytes protects the poststenotic mouse kidney from ischemic injury, underscoring the therapeutic potential role of pericytes in subjects with ischemic kidney disease. Our study demonstrates a novel pericyte-based therapy for the injured kidney. The beneficial effect of pericyte delivery appears to be mediated by ameliorating oxidative stress, inflammation, cellular apoptosis, and senescence in the stenotic kidney and improved tissue hypoxia, vascular loss, fibrosis, and tubular atrophy. Our data may form the basis for pericyte-based therapy, and additional research studies are needed to gain further insight into their role in improving renal function.
周细胞被认为是具有修复功能的间充质干细胞样细胞，但它们改善慢性缺血性肾损伤的能力尚不清楚。我们假设周细胞在小鼠肾动脉狭窄（RAS）中会表现出肾保护作用。在诱导单侧 RAS 后 2 周，将猪肾来源的周细胞（5×10）或载体注射到颈动脉中。2 周后，使用磁共振成像测量狭窄肾脏的肾小球滤过率和组织氧合。随后，我们比较了肾脏的氧化应激、炎症、细胞凋亡、纤维化以及系统中氧化和炎症细胞因子的水平。异种周细胞的治疗改善了 RAS 引起的灌注、肾小球滤过率和狭窄肾脏的萎缩，并恢复了皮质和髓质的氧合作用，但并未缓解高血压。在体外，周细胞注射部分减轻了 RAS 引起的肾脏炎症、纤维化、氧化应激、细胞凋亡和衰老。此外，体外共培养周细胞可保护猪肾 1 管状细胞免受损伤。总之，外源性肾周细胞的输送可保护后狭窄期的小鼠肾脏免受缺血性损伤，突出了周细胞在缺血性肾病患者中的治疗潜力。我们的研究为受损肾脏提供了一种新的周细胞治疗方法。周细胞输送的有益效果似乎是通过改善狭窄肾脏的氧化应激、炎症、细胞凋亡和衰老，以及改善组织缺氧、血管丢失、纤维化和管状萎缩来介导的。我们的数据可能为基于周细胞的治疗奠定基础，还需要进一步的研究来更深入地了解它们在改善肾功能方面的作用。
