BackgroundMesenchymal stromal cells (MSCs) represent an option for the treatment of acute kidney injury (AKI). It is known that young stem cells are better than are aged stem cells at reducing the incidence of the senescent phenotype in the kidneys. The objective of this study was to determine whether AKI leads to premature, stress-induced senescence, as well as whether human umbilical cord-derived MSCs (huMSCs) can prevent ischaemia/reperfusion injury (IRI)-induced renal senescence in rats.MethodsBy clamping both renal arteries for 45 min, we induced IRI in male rats. Six hours later, some rats received 1 × 106 huMSCs or human adipose-derived MSCs (aMSCs) intraperitoneally. Rats were euthanised and studied on post-IRI days 2, 7 and 49.ResultsOn post-IRI day 2, the kidneys of huMSC-treated rats showed improved glomerular filtration, better tubular function and higher expression of aquaporin 2, as well as less macrophage infiltration. Senescence-related proteins (β-galactosidase, p21Waf1/Cip1, p16INK4a and transforming growth factor beta 1) and microRNAs (miR-29a and miR-34a) were overexpressed after IRI and subsequently downregulated by the treatment. The IRI-induced pro-oxidative state and reduction in Klotho expression were both reversed by the treatment. In comparison with huMSC treatment, the treatment with aMSCs improved renal function to a lesser degree, as well as resulting in a less pronounced increase in the renal expression of Klotho and manganese superoxide dismutase. Treatment with huMSCs ameliorated long-term kidney function after IRI, minimised renal fibrosis, decreased β-galactosidase expression and increased the expression of Klotho.ConclusionsOur data demonstrate that huMSCs attenuate the inflammatory and oxidative stress responses occurring in AKI, as well as reducing the expression of senescence-related proteins and microRNAs. Our findings broaden perspectives for the treatment of AKI.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0475-8) contains supplementary material, which is available to authorized users.

Dedico este trabalho a:Deus, que me permitiu fazer parte de uma família tão maravilhosa e percorrer o caminho do aprendizado e das conquistas para a realização deste trabalho.Meus pais Manoel e Luzia que com muito amor me ensinaram a conhecê-Lo e amá-Lo em todas as coisas, e me orientaram para que eu pudesse seguir o caminho para a busca permanente da verdade.Minha irmã Gisele que me mostrou o quanto pode haver de amor nas diferenças e possibilitou conviver com seu filho tão querido, Pedro José.Alexandre, meu grande companheiro, que com muito amor e abnegação adiou projetos e momentos de sua vida, passou por situações únicas com nosso bebê para a realização deste trabalho.Meu querido filho João Guilherme que, com a pureza de seu amor, a cada dia me mostra, na forma mais perfeita, a existência de Deus. AGRADECIMENTOS