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BM-MSC-derived small extracellular vesicles (sEV) from trained animals presented nephroprotective potential in unilateralureteral obstruction model

Rafael da Silva Luiz1, Rodolfo Rosseto Rampaso1, Alef Aragão Carneiro dos Santos2, Marcia Bastos Convento1, Dulce Aparecida Barbosa3, Cassiane Dezoti da Fonseca3, Andréia Silva de Oliveira1, Agnaldo Caires1, Andrei Furlan1, Nestor Schor1, Fernanda Teixeira Borges1,2 [ + show more ]

J Venom Anim Toxins incl Trop Dis, 2021, 27:e20200187
Received: 14 December 2020 | Accepted: 21 May 2021 | Published online: 03 December 2021
Collection: Inflammation: from bench to bedside


Background: The efficacy of bone marrow mesenchymal stromal cells (BM-MSC) and its extracellular vesicles has been demonstrated for a broad spectrum of indications, including kidney diseases. However, BM-MSC donor characteristics and their potential are not usually considered. Therefore, the present work aims to evaluate the nephroprotective capacity of sEV secreted by BM-MSC from trained rats inunilateral ureteral obstruction (UUO) model. Methods: BM-MSC was characterized by their differentiation potential and immunophenotypic markers. The sEV were isolated by ultracentrifugation and characterized by nanoparticle tracking analysis and western blot. Its miRNA cargo was examined by quantitative PCR analysis for miR-26a, 126a, and 296. Wistar rats were submitted to UUO procedure and concomitantly treated with sEV secreted by BM-MSC from the untrained andtrained rats. The kidney tissue from all groups was evaluated for fibrosis mediators (transforming growth factor beta1 and collagen), CD34-angiogenesis marker, and hypoxia-inducible factor 1 alpha (HIF-1α). Results: Treadmill training stimulated in BM-MSC the production of sEV loaded with pro-angiogenic miR-296. The treatment with this sEVin UUO-rats was able to attenuate collagen accumulation and increase CD34 and HIF-1α in the kidney tissue when compared to untrained ones. Tubular proximal cells under hypoxia and exposed to BM-MSC sEV demonstrate accumulation in HIF-1α and NFR-2 (nuclear factor erythroid 2-related factor 2), possibly to mediate the response to hypoxia and oxidative stress, under these conditions. Conclusion: The BM-MSC sEV from trained animals presented an increased nephroprotective potential compared to untrained vesicles by carrying 296-angiomiR and contributing to angiogenesis in UUO model.


Keywords: Chronic kidney disease; Physical activity; Bone marrow mesenchymal stromal cells; Small extracellular vesicles; Angiogenesis.

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