Mesenchymal stem cells protective effect in adriamycin model of nephropathy.
Mesenchymal stem cells (MSCs) may be of value in regeneration of renal tissue after damage; however, lack of biological knowledge and variability of results in animal models limit their utilization. We studied the effects of MSCs on podocytes in vitro and in vivo utilizing adriamycin (ADR) as a model of renal toxicity. The in vivo experimental approach was carried out in male Sprague-Dawley rats (overall 60 animals) treated with different ADR schemes to induce acute and chronic nephrosis. MSCs were given a) concomitantly to ADR in tail vein or b) in aorta and c) in tail vein 60 days after ADR. Homing was assessed with PKH26-MSCs. MSCs rescued podocytes from apoptosis induced by ADR in vitro. The maximal effect (80% rescue) was obtained with MSCs/podocytes coculture ratio of 1:1 for 72 h. All rats treated with ADR developed nephrosis. MSCs did not modify the clinical parameters (i.e., proteinuria, serum creatinine, lipids) but protected the kidney from severe glomerulosclerosis when given concomitantly to ADR. Rats given MSCs 60 days after ADR developed the same severe renal damage. Only a few MSCs were found in renal tubule-interstitial areas 1-24 h after injection and no MSCs were detected in glomeruli. MSCs reduced apoptosis of podocytes treated with ADR in vitro. Early and repeated MSCs infusion blunted glomerular damage in chronic ADR-induced nephropathy. MSCs did not modify proteinuria and progression to renal failure, which implies lack of regenerative potential in this model.
Magnasco
Alberto
A
Department of Nephrology, G. Gaslini Children Hospital, Genoa, Italy.
Corselli
Mirko
M
Bertelli
Roberta
R
Ibatici
Adalberto
A
Peresi
Monica
M
Gaggero
Gabriele
G
Cappiello
Valentina
V
Chiavarina
Barbara
B
Mattioli
Girolamo
G
Gusmano
Rosanna
R
Ravetti
Jean Louis
JL
Frassoni
Francesco
F
Ghiggeri
Gian Marco
GM
D000818:Animals; D000903:Antibiotics, Antineoplastic; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D002908:Chronic Disease; D019610:Cytoprotection / Q000502:physiology; D004195:Disease Models, Animal; D004317:Doxorubicin; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D050199:Podocytes / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin