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Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles Elicit Better Preservation of the Intra-Renal Microvasculature Than Renal Revascularization in Pigs with Renovascular Disease

1
Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55901, USA
2
Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55901, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Alexander E. Kalyuzhny
Cells 2021, 10(4), 763; https://doi.org/10.3390/cells10040763
Received: 26 February 2021 / Revised: 23 March 2021 / Accepted: 30 March 2021 / Published: 31 March 2021
Background: Percutaneous transluminal renal angioplasty (PTRA) confers clinical and mortality benefits in select ‘high-risk’ patients with renovascular disease (RVD). Intra-renal-delivered extracellular vesicles (EVs) released from mesenchymal stem/stromal cells (MSCs) protect the kidney in experimental RVD, but have not been compared side-by-side to clinically applied interventions, such as PTRA. We hypothesized that MSC-derived EVs can comparably protect the post-stenotic kidney via direct tissue effects. Methods: Five groups of pigs (n = 6 each) were studied after 16 weeks of RVD, RVD treated 4 weeks earlier with either PTRA or MSC-derived EVs, and normal controls. Single-kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were assessed in vivo with multi-detector CT, and renal microvascular architecture (3D micro CT) and injury pathways ex vivo. Results: Despite sustained hypertension, EVs conferred greater improvement of intra-renal microvascular and peritubular capillary density compared to PTRA, associated with attenuation of renal inflammation, oxidative stress, and tubulo-interstitial fibrosis. Nevertheless, stenotic kidney RBF and GFR similarly rose in both PTRA- and EV-treated pigs compared RVD + Sham. mRNA sequencing reveled that EVs were enriched with pro-angiogenic, anti-inflammatory, and antioxidants genes. Conclusion: MSC-derived EVs elicit a better preservation of the stenotic kidney microvasculature and greater attenuation of renal injury and fibrosis compared to PTRA, possibly partly attributed to their cargo of vasculo-protective genes. Yet, both strategies similarly improve renal hemodynamics and function. These observations shed light on diverse mechanisms implicated in improvement of post-stenotic kidney function and position EVs as a promising therapeutic intervention in RVD. View Full-Text
Keywords: renovascular disease; microvasculature; revascularization; mesenchymal stem/stromal cells; extracellular vesicles renovascular disease; microvasculature; revascularization; mesenchymal stem/stromal cells; extracellular vesicles
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MDPI and ACS Style

Ferguson, C.M.; Farahani, R.A.; Zhu, X.-Y.; Tang, H.; Jordan, K.L.; Saadiq, I.M.; Lerman, A.; Lerman, L.O.; Eirin, A. Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles Elicit Better Preservation of the Intra-Renal Microvasculature Than Renal Revascularization in Pigs with Renovascular Disease. Cells 2021, 10, 763. https://doi.org/10.3390/cells10040763

AMA Style

Ferguson CM, Farahani RA, Zhu X-Y, Tang H, Jordan KL, Saadiq IM, Lerman A, Lerman LO, Eirin A. Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles Elicit Better Preservation of the Intra-Renal Microvasculature Than Renal Revascularization in Pigs with Renovascular Disease. Cells. 2021; 10(4):763. https://doi.org/10.3390/cells10040763

Chicago/Turabian Style

Ferguson, Christopher M.; Farahani, Rahele A.; Zhu, Xiang-Yang; Tang, Hui; Jordan, Kyra L.; Saadiq, Ishran M.; Lerman, Amir; Lerman, Lilach O.; Eirin, Alfonso. 2021. "Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles Elicit Better Preservation of the Intra-Renal Microvasculature Than Renal Revascularization in Pigs with Renovascular Disease" Cells 10, no. 4: 763. https://doi.org/10.3390/cells10040763

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