title: Mesenchymal stem cells in renal function recovery after acute kidney injury: use of a differentiating agent in a rat model.
abstract: Acute kidney injury (AKI) is a major health care condition with limited current treatment options. Within this context, stem cells may provide a clinical approach for AKI. Moreover, a synthetic compound previously developed, hyaluronan monoesters with butyric acid (HB), able to induce  metanephric differentiation, formation of capillary-like structures, and secretion of angiogenic cytokines, was tested in vitro. Thereafter, we investigated the effects of human mesenchymal stem cells from fetal membranes (FMhMSCs), both treated and untreated with HB, after induction of ischemic  AKI in a rat model. At reperfusion following 45-min clamping of renal pedicles, each rat was randomly assigned to one of four groups: CTR, PBS, MSC, and MSC-HB. Renal function at 1, 3, 5, and 7 days was assessed. Histological samples were analyzed by light and electron microscopy and renal  injury was graded. Cytokine analysis on serum samples was performed. FMhMSCs induced an accelerated renal functional recovery, demonstrated by biochemical parameters and confirmed by histology showing that histopathological alterations associated with ischemic injury were less severe in cell-treated  kidneys. HB-treated rats showed a minor degree of inflammation, both at cytokine and TEM analyses. Better functional and morphological recovery were not associated to stem cells' regenerative processes, but possibly suggest paracrine effects on microenvironment that induce retrieval of renal  damaged tissues. These results suggest that FMhMSCs could be useful in the treatment of AKI and the utilization of synthetic compounds could enhance the recovery induction ability of cells.
authors.affiliation: Department of Internal Medicine, Aging and Renal Disease-Section of Nephrology, University of Bologna, Bologna, Italy. gaetano.lamanna@unibo.it
authors.forename: Gaetano
authors.initials: G
authors.lastname: La Manna
authors.forename: Francesca
authors.initials: F
authors.lastname: Bianchi
authors.forename: Maria
authors.initials: M
authors.lastname: Cappuccilli
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cenacchi
authors.forename: Lucia
authors.initials: L
authors.lastname: Tarantino
authors.forename: Gianandrea
authors.initials: G
authors.lastname: Pasquinelli
authors.forename: Sabrina
authors.initials: S
authors.lastname: Valente
authors.forename: Elena
authors.initials: E
authors.lastname: Della Bella
authors.forename: Silvia
authors.initials: S
authors.lastname: Cantoni
authors.forename: Cavallini
authors.initials: C
authors.lastname: Claudia
authors.forename: Flavia
authors.initials: F
authors.lastname: Neri
authors.forename: Matvey
authors.initials: M
authors.lastname: Tsivian
authors.forename: Bruno
authors.initials: B
authors.lastname: Nardo
authors.forename: Carlo
authors.initials: C
authors.lastname: Ventura
authors.forename: Sergio
authors.initials: S
authors.lastname: Stefoni
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000503:physiopathology* / Q000628:therapy*; D000818:Animals; D020148:Butyric Acid / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D007677:Kidney Function Tests; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*
chemical_list: D016207:Cytokines; D020148:Butyric Acid; D006820:Hyaluronic Acid