Exogenous pericyte delivery protects the mouse kidney from chronic ischemic injury

Objective: Pericytes are considered as reparative mesenchymal stem cell (MSC)-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). Methods: Porcine kidney-derived pericytes (5×105) or vehicle were injected into the aorta two weeks after induction of unilateral RAS in mice. Stenotic-kidney glomerular filtration rate (GFR) and tissue oxygenation were measured 2 weeks later using magnetic-resonance-imaging. We subsequently compared kidney oxidative stress, inflammation, apoptosis, and fibrosis, and systemic levels of oxidative and inflammatory cytokines. Results: Xenogeneic pericytes treatment ameliorates the RAS-induced loss of perfusion, GFR, and atrophy in stenotic kidneys, restored cortical and medullary oxygenation, but did not blunt hypertension. Ex vivo, pericytes injection partially mitigated the RAS induced renal inflammation, fibrosis, oxidative stress, apoptosis, and senescence. Furthermore, co-culture with pericytes in vitro protected pig-kidney-1 tubular cells from injury. Conclusion: Exogenous delivery of renal pericytes protects the post-stenotic mouse kidney from ischemic injury, underscoring the therapeutic potential role of pericytes in subjects with ischemic kidney disease.

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