Mesenchymal stromal cells improve renal injury in anti-Thy 1 nephritis by modulating inflammatory cytokines and scatter factors

Abstract

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.

Allogenic fetal membrane-derived mesenchymal stem cells contribute to renal repair in experimental glomerulonephritis

“…Our previous studies found that FM-and BM-MSC secreted VEGF and HGF, which are well-known potent angiogenic and antiapoptotic factors that elicited angiogenesis in a hindlimb ischemia model (20). In experimental ischemic acute kidney injury or glomerulonephritis, VEGF or HGF secreted from MSC exerted beneficial effects (31,46,56,58). Based on these results, we examined the glomerular expression of these regenerative factors in anti-Thy1 nephritic rats.…”

Stem Cell-Based Cell Therapy for Glomerulonephritis

“…Many studies have shown that BM-MSC treatment could improve the renal function and histological changes, by reducing mononuclear infiltration, attenuating mesangial activation and glomerular endocapillary proliferation [18, 19, 52]. Tsuda et al have reported that in the anti-Thy 1 nephritis rats FM-MSCs could significantly reduce activated mesangial cell proliferation, glomerular monocyte/macrophage infiltration, mesangial matrix accumulation, and the glomerular expression of inflammatory or extracellular matrix-related genes including TNF- α , monocyte chemotactic protein-1 (MCP-1), type I collagen, TGF- β , and type 1 plasminogen activator inhibitor (PAI-1) [22].…”

“…It is found that MSCs could suppress glomerular MSP and Ron expression and decrease the local level of platelet-derived growth factor β (PDGF- β ) and circulating level of TGF- β . This effect of reduction of infiltrating monocytes promotes the attenuation of glomerular injury [18]. …”

“…Such stabilization was associated with levels of PDGF- β , MSP, and IL-6 lower than in untreated rats. Rampino et al suggested that MSCs regulate the repair response driven by PDGF- β , MSP, and IL-6, making glomerular proliferation less aggressive and more steady [18]. In ADR nephropathy, Zoja et al showed that repeated MSC injections by exerting a remarkable antiapoptotic effect limited podocyte depletion and partially restored nephrin and CD2AP expression.…”

“…In anti-Thy 1 disease, the lysis of the mesangial stalk causes loss of glomerular capillaries, rarefaction of the capillary network and formation of microaneurysms [18]. The reconstruction of new glomerular capillaries is necessary for wound healing.…”