Selective intrarenal delivery of mesenchymal stem cell-derived extracellular vesicles attenuates myocardial injury in experimental metabolic renovascular disease.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Extracellular vesicles (EVs) deliver genes and proteins to recipient cells, and mediate paracrine actions of their parent cells. Intrarenal delivery of mesenchymal stem cell (MSC)-derived EVs preserves stenotic-kidney function and reduces release of pro-inflammatory cytokines in a swine model of coexisting metabolic syndrome (MetS) and renal artery stenosis (RAS). We hypothesized that this approach is also capable of blunting cardiac injury and dysfunction. Five groups of pigs were studied after 16 weeks of diet-induced MetS and RAS (MetS + RAS), MetS and MetS + RAS treated 4 weeks earlier with a single intrarenal delivery of EVs-rich fraction harvested from autologous adipose tissue-derived MSCs, and lean and MetS Shams. Cardiac structure, function, and myocardial oxygenation were assessed in vivo using imaging, and cardiac inflammation, senescence, and fibrosis ex vivo. Inflammatory cytokine levels were measured in circulating and renal vein blood. Intrarenal EV delivery improved stenotic-kidney glomerular filtration rate and renal blood flow, and decreased renal release of monocyte-chemoattractant protein-1 and interleukin-6. Furthermore, despite unchanged systemic hemodynamics, intrarenal EV delivery in MetS + RAS normalized cardiac diastolic function, attenuated left ventricular remodeling, cellular senescence and inflammation, and improved myocardial oxygenation and capil

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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