Extracellular vesicles released by adipose tissue-derived mesenchymal stromal/stem cells from obese pigs fail to repair the injured kidney.

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)

Mesenchymal stromal/stem cell (MSC)-derived extracellular vesicles (EVs) shuttle select MSC contents and are endowed with an ability to repair ischemic tissues. We hypothesized that exposure to cardiovascular risk factors may alter the microRNA cargo of MSC-derived EVs, blunting their capacity to repair the post-stenotic kidney in pigs with metabolic syndrome (MetS) and renal artery stenosis (RAS). Porcine MSCs were harvested from abdominal fat after 16wks of Lean- or MetS-diet, and their EVs isolated and characterized using microRNA-sequencing. Lean- and MetS-EV protective effects were assessed in-vitro in human umbilical endothelial cells (HUVECs). To compare their in-vivo efficacy to repair ischemic tissues, allogeneic-EVs were intrarenally delivered in pigs after 6wks of MetS + RAS, and 4wks later, single-kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were studied in-vivo, and microvascular architecture and injury ex-vivo. Lean-, MetS-, and MetS + RAS-sham served as controls (n = 6 each). Ten microRNAs, capable of targeting several pro-angiogenic genes, were upregulated in MetS-EVs versus Lean-EVs. In vitro, MetS-EVs failed to increase tube number and length, and to boost HUVEC migration compared to Lean-EVs. Lean- and MetS-EVs were detected in the stenotic-kidney 4wks after injection in the vicinity of small vessels. RBF and GFR were lower in MetS + RAS

Evidence level

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

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.