title: Human bone marrow mesenchymal stem cells accelerate recovery of acute renal injury and prolong survival in mice.
abstract: Transplantation of bone marrow mesenchymal stem cells (BM-MSC) or stromal cells from rodents has been identified as a strategy for renal repair in experimental models of acute kidney injury (AKI), a highly life-threatening clinical setting. The therapeutic potential of BM-MSC of human origin has not been reported so far. Here, we investigated whether human BM-MSC treatment could prevent AKI induced by cisplatin and prolong survival in an immunodeficient mouse model. Results showed that human BM-MSC infusion decreased proximal tubular epithelial cell injury and ameliorated the deficit in renal function, resulting in reduced recipient mortality. Infused BM-MSC became localized predominantly in peritubular areas and acted to reduce renal cell apoptosis and to increase proliferation. BM-MSC also induced protection against AKI-related peritubular capillary changes consisting of endothelial cell abnormalities, leukocyte infiltration, and low endothelial cell and lumen volume density as assessed by morphometric analysis. These findings indicate that human MSC of bone marrow origin hold potential to prolong survival in AKI and should be considered for testing in a clinical trial. Disclosure of potential conflicts of interest is found at the end of this article.
authors.affiliation: "Mario Negri" Institute for Pharmacological Research, Via Gavazzeni 11, 24125 Bergamo, Italy. morigi@marionegri.it
authors.forename: Marina
authors.initials: M
authors.lastname: Morigi
authors.forename: Martino
authors.initials: M
authors.lastname: Introna
authors.forename: Barbara
authors.initials: B
authors.lastname: Imberti
authors.forename: Daniela
authors.initials: D
authors.lastname: Corna
authors.forename: Mauro
authors.initials: M
authors.lastname: Abbate
authors.forename: Cinzia
authors.initials: C
authors.lastname: Rota
authors.forename: Daniela
authors.initials: D
authors.lastname: Rottoli
authors.forename: Ariela
authors.initials: A
authors.lastname: Benigni
authors.forename: Norberto
authors.initials: N
authors.lastname: Perico
authors.forename: Carla
authors.initials: C
authors.lastname: Zoja
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
authors.forename: Andrea
authors.initials: A
authors.lastname: Remuzzi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology; D005260:Female; D006801:Humans; D007668:Kidney / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D016513:Mice, SCID; D010641:Phenotype
chemical_list: D002945:Cisplatin