Mesenchymal stromal cells improve renal injury in anti-Thy 1 nephritis by modulating inflammatory cytokines and scatter factors.
MSC (mesenchymal stromal cells) can differentiate into renal adult cells, and have anti-inflammatory and immune-modulating activity. In the present study, we investigated whether MSC have protective/reparative effects in anti-Thy1 disease, an Ab (antibody)-induced mesangiolysis resulting in mesangioproliferative nephritis. We studied five groups of rats: (i) rats injected with anti-Thy1.1 Ab on day 0 (group A); (ii) rats injected with anti-Thy1.1 Ab on day 0+MSC on day 3 (group B); (iii) rats injected with anti-Thy1.1 Ab on day 0+mesangial cells on day 3 (group C); (iv) rats injected with saline on day 0+MSC on day 3 (group D); and (v) rats injected with saline on day 0 (group E). Rats were killed on days 1, 3, 7 and 14. MSC prevented the increase in serum creatinine, proteinuria, glomerular monocyte influx and glomerular histopathological injury. Furthermore, MSC suppressed the release of IL-6 (interleukin-6) and TGF-β (transforming growth factor-β), modulated glomerular PDGF-β (platelet-derived growth factor-β), and reset the scatter factors and their receptors, potentiating HGF (hepatocyte growth factor)/Met and inactivating MSP (macrophage-stimulating protein)/Ron (receptor origin nantaise). Few MSC were found in the kidney. These results indicate that MSC improve anti-Thy 1 disease not by replacing injured cells, but by preventing cytokine-driven inflammation and modulating PDGF-β and the scatter factors, i.e. systems that regulate movement and proliferation of monocytes and mesangial cells.
Rampino
Teresa
T
Unit of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo and University of Pavia, 27100 Pavia, Italy.
Gregorini
Marilena
M
Bedino
Giulia
G
Piotti
Giovanni
G
Gabanti
Elisa
E
Ibatici
Adalberto
A
Sessarego
Nadia
N
Piacenza
Cristina
C
Balenzano
Chiara Teresa
CT
Esposito
Pasquale
P
Bosio
Francesca
F
Soccio
Grazia
G
Frassoni
Francesco
F
Dal Canton
Antonio
A
D000818:Animals; D002478:Cells, Cultured; D003176:Complement C3 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005921:Glomerulonephritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017154:Stromal Cells / Q000637:transplantation*; D018800:Thy-1 Antigens / Q000276:immunology
D003176:Complement C3; D016207:Cytokines; D018836:Inflammation Mediators; D018800:Thy-1 Antigens; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases