title: Proregenerative Microenvironment Triggered by Donor Mesenchymal Stem Cells Preserves Renal Function and Structure in Mice with Severe Diabetes Mellitus.
abstract: The aim of our work was to evaluate, in an animal model of severe diabetes mellitus, the effect of mesenchymal stem cells (MSCs) administration on diabetic nephropathy (DN) progression. After diabetes induction, one group of mice received the vehicle (DM) and other group received a single dose of MSCs (DM + MSCs). DM + MSCs mice showed a significant improvement in functional parameters of the kidney compared with untreated mice. While DM mice presented marked histopathological changes characteristics of advanced stages of DN (fibrosis, glomerulosclerosis, glomerular basement membrane thickening, capillary occlusion, decreased podocyte density, and effacement of foot processes), DM + MSCs mice showed only slight tubular dilatation. The renoprotection was not associated with an improvement in diabetic condition and very low number of donor cells was found in the kidney of DM + MSCs mice, suggesting that renoprotection could be mediated by paracrine effects. Indeed, DM + MSC mice presented increased renal proliferation index, decreased renal apoptotic index and the restoration of proregenerative factors, and anti-inflammatory cytokines levels. Moreover, macrophage infiltration and oxidative stress damage were also reduced in DM + MSCs mice. Our data demonstrate that MSC administration triggers a proregenerative microenvironment in DN kidney, which allows the preservation of the renal function even if diabetes was uncorrected.
authors.affiliation: Centro de Medicina Regenerativa, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Avenida Las Condes 12438, Santiago, Chile.
authors.forename: Fernando
authors.initials: F
authors.lastname: Ezquer
authors.affiliation: Centro de Medicina Regenerativa, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Avenida Las Condes 12438, Santiago, Chile ; Laboratorio de Fisiología (IHEM-CONICET) and Instituto de Fisiología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Casilla de Correo 33, Mendoza, Argentina.
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Giraud-Billoud
authors.affiliation: Instituto de Anatomía, Histología y Patología, Facultad de Medicina Universidad Austral de Chile, Isla Teja s/n, Valdivia, Chile.
authors.forename: Daniel
authors.initials: D
authors.lastname: Carpio
authors.affiliation: Centro de Medicina Regenerativa, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Avenida Las Condes 12438, Santiago, Chile ; Facultad de Ciencias Biológicas, Universidad Andrés Bello, Avenida Los Leones 745, Santiago, Chile.
authors.forename: Fabián
authors.initials: F
authors.lastname: Cabezas
authors.affiliation: Centro de Medicina Regenerativa, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Avenida Las Condes 12438, Santiago, Chile.
authors.forename: Paulette
authors.initials: P
authors.lastname: Conget
authors.affiliation: Centro de Medicina Regenerativa, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Avenida Las Condes 12438, Santiago, Chile.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Ezquer
mesh_terms: D000818:Animals; D060833:Cellular Microenvironment; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology* / Q000517:prevention & control; D007668:Kidney / Q000473:pathology / Q000502:physiology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL