Life-sparing effect of human cord blood-mesenchymal stem cells in experimental acute kidney injury.
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.
Morigi
Marina
M
Mario Negri Institute for Pharmacological Research, Bergamo, Italy. morigi@marionegri.it
Rota
Cinzia
C
Montemurro
Tiziana
T
Montelatici
Elisa
E
Lo Cicero
Viviana
V
Imberti
Barbara
B
Abbate
Mauro
M
Zoja
Carla
C
Cassis
Paola
P
Longaretti
Lorena
L
Rebulla
Paolo
P
Introna
Martino
M
Capelli
Chiara
C
Benigni
Ariela
A
Remuzzi
Giuseppe
G
Lazzari
Lorenza
L
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
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D051057:Proto-Oncogene Proteins c-akt