Mesenchymal stromal cells improve renal injury in anti-Thy 1 nephritis by modulating inflammatory cytokines and scatter factors.
Résumé
Mesenchymal Stromal Cells (MSC) can differentiate into renal adult cells, and have anti-inflammatory and immune-modulating activity. We investigated whether MSC have protective/reparative effects in anti-Thy 1 disease, an antibody-induced mesangiolysis resulting in mesangioproliferative nephritis. We studied five groups of rats. A: rats injected with anti-Thy Ab on day 0. B: rats injected with anti-Thy Ab on day 0 + MSC on day 3. C: rats injected with anti-Thy Ab on day 0 + mesangial cells on day 3. D: rats injected with saline on day 0 + MSC on day 3. E: rats injected with saline on day 0. Rats were sacrificed on days 1, 3, 7, 14. MSC prevented the rise in serum creatinine, proteinuria, glomerular monocyte influx and glomerular histopathological injury. Furthermore, MSC suppressed release of interleukin-6 (IL-6) and transforming growth factor-β (TGF-β), modulated glomerular platelet-derived growth factor-β ( (PDGF-β), and reset the Scatter Factors and their receptors, potentiating hepatocyte growth factor (HGF)/Met and inactivating macrophage stimulating protein (MSP)/Ron. Rare 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.
Origine : Fichiers produits par l'(les) auteur(s)
Loading...