title: Life-sparing effect of human cord blood-mesenchymal stem cells in experimental acute kidney injury.
abstract: In search for new sources of mesenchymal stem cells (MSCs) for renal repair in acute kidney injury (AKI), we investigated the potential of human cord blood (CB)-MSCs to cure mice with AKI. Infusion of CB-MSCs in immunodeficient mice with cisplatin-induced AKI ameliorated both renal function and tubular cell injury, and prolonged survival. Transplanted CB-MSCs localized in peritubular areas, limited capillary alterations and neutrophil infiltration. Apoptosis reduced and tubular cell proliferation increased by virtue of stem cell capacity to produce growth factors. The reno-protective effect of CB-MSCs was further confirmed by their ability to inhibit oxidative damage and to induce the prosurvival factor Akt in tubular cells. The evidence that CB-MSCs in vitro increased the production of growth factors and inhibited IL-1 beta and TNFalpha synthesis when cocultured with damaged proximal tubular cells indicates a regenerative and anti-inflammatory action of stem cell treatment. Altogether these results highlight the potential of human CB-MSCs as future cell therapy for testing in human AKI.
authors.affiliation: Mario Negri Institute for Pharmacological Research, Bergamo, Italy. morigi@marionegri.it
authors.forename: Marina
authors.initials: M
authors.lastname: Morigi
authors.forename: Cinzia
authors.initials: C
authors.lastname: Rota
authors.forename: Tiziana
authors.initials: T
authors.lastname: Montemurro
authors.forename: Elisa
authors.initials: E
authors.lastname: Montelatici
authors.forename: Viviana
authors.initials: V
authors.lastname: Lo Cicero
authors.forename: Barbara
authors.initials: B
authors.lastname: Imberti
authors.forename: Mauro
authors.initials: M
authors.lastname: Abbate
authors.forename: Carla
authors.initials: C
authors.lastname: Zoja
authors.forename: Paola
authors.initials: P
authors.lastname: Cassis
authors.forename: Lorena
authors.initials: L
authors.lastname: Longaretti
authors.forename: Paolo
authors.initials: P
authors.lastname: Rebulla
authors.forename: Martino
authors.initials: M
authors.lastname: Introna
authors.forename: Chiara
authors.initials: C
authors.lastname: Capelli
authors.forename: Ariela
authors.initials: A
authors.lastname: Benigni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
authors.forename: Lorenza
authors.initials: L
authors.lastname: Lazzari
mesh_terms: D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D018920:Coculture Techniques; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007668:Kidney / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D007674:Kidney Diseases / Q000503:physiopathology / Q000601:surgery*; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D018384:Oxidative Stress / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D051057:Proto-Oncogene Proteins c-akt