title: Bone marrow-derived mesenchymal stem cells repaired but did not prevent gentamicin-induced acute kidney injury through paracrine effects in rats.
abstract: This study evaluated the effects of bone marrow-derived mesenchymal stem cells (BMSCs) or their conditioned medium (CM) on the repair and prevention of Acute Kidney Injury (AKI) induced by gentamicin (G). Animals received daily injections of G up to 20 days. On the 10(th) day, injections of BMSCs, CM, CM+trypsin, CM+RNase or exosome-like microvesicles extracted from the CM were administered. In the prevention groups, the animals received the BMSCs 24 h before or on the 5(th) day of G treatment. Creatinine (Cr), urea (U), FENa and cytokines were quantified. The kidneys were evaluated using hematoxylin/eosin staining and immunohystochemistry. The levels of Cr, U and FENa increased during all the periods of G treatment. The BMSC transplantation, its CM or exosome injections inhibited the increase in Cr, U, FENa, necrosis, apoptosis and also increased cell proliferation. The pro-inflammatory cytokines decreased while the anti-inflammatory cytokines increased compared to G. When the CM or its exosomes were incubated with RNase (but not trypsin), these effects were blunted. The Y chromosome was not observed in the 24-h prevention group, but it persisted in the kidney for all of the periods analyzed, suggesting that the injury is necessary for the docking and maintenance of BMSCs in the kidney. In conclusion, the BMSCs and CM minimized the G-induced renal damage through paracrine effects, most likely through the RNA carried by the exosome-like microvesicles. The use of the CM from BMSCs can be a potential therapeutic tool for this type of nephrotoxicity, allowing for the avoidance of cell transplantations.
authors.affiliation: Nephrology Division, Department of Medicine, UNIFESP/EPM, São Paulo, Brazil.
authors.forename: Luciana A
authors.initials: LA
authors.lastname: Reis
authors.forename: Fernanda T
authors.initials: FT
authors.lastname: Borges
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Simões
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Borges
authors.forename: Rita
authors.initials: R
authors.lastname: Sinigaglia-Coimbra
authors.forename: Nestor
authors.initials: N
authors.lastname: Schor
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control* / Q000628:therapy*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D055354:Exosomes / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005839:Gentamicins / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019899:Paracrine Communication / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing / Q000187:drug effects
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D005839:Gentamicins