Effect of Mesenchymal STEM CELLS and Their Secretome on Renal Progenitors CELLS in MODEL LPS Nephrotoxicity.

We investigated the effects of mesenchymal stem cells (MSCs), your conditioned medium (CM) or exosomes (EXOs) in a LPS-induced nephrotoxicity and the role of renal stem progenitor cells (RPCs) in this model. Rats received i.v.: LPS (10 mg/Kg B.W.) or PBS (CTL) with MSCs (1x106), CM (500 µl) or its EXOs (100 µg/ml) from MSCs incubated or not for 12 hours with cytochalasin B (CB; 1 µM) or actinomycin D (AD; 2.6 µM), given in 1 or 3 administrations, sacrificed after 72 hours. Blood, urine samples were collected for creatinine (sCr), urea (sU) and FENa. Kidneys were analyzed for HE, KI67, caspase 3. EXOs as CD63and TEM. Y chromosome, IL6, TNF-α, INF-γ and IL10 were evaluated and RPCs for Wnt1, BrDU, PAX2, CD24. It was observed increases in sCr, sU, FENa, caspase 3 marking, proinflammatory cytokines and reduction of KI67 with lesions in proximal tubules by LPS. These parameters were ameliorated with MSCs, CM or EXOs. LPS and LPS+EXOs increased BrDU, Wnt1, PAX2, CD24 and CD63 expressions indicating positive mark of RPCs. CB and AD inhibited the protective effect of EXOs. The effect of 3 administrations of MSCs or CM or EXOs decreased mortality in LPS. Therefore, results support that the MSCs and its CM and EXOs protected from LPS-nephrotoxicity. It is reasonable to suggest that the mediation by EXOs at least in part, by expression RPCs in this cascade of events and finally, those EXOs alone could be employed in order to ameliorate LPS acute kidney injury (AKI). 

Funds from: FAPESP, CNPq, CAPES and FOR