Bone-Marrow-Derived Cells Contribute to Glomerular Endothelial Repair in Experimental Glomerulonephritis

Abstract

Glomerular endothelial injury plays an important role in the pathogenesis of renal diseases and is centrally involved in renal disease progression. Glomerular endothelial repair may help maintain renal function. We examined whether bone-marrow (BM)-derived cells contribute to glomerular repair. A rat allogenic BM transplant model was used to allow tracing of BM-derived cells using a donor major histocompatibility complex class-I specific mAb. In glomeruli of chimeric rats we identified a small number of donor-BM-derived endothelial and mesangial cells, which increased in a time-dependent manner. Induction of anti-Thy-1.1-glomerulonephritis (transient mesangial and secondary glomerular endothelial injury) caused a significant, more than fourfold increase in the number of BM-derived glomerular endothelial cells at day 7 after anti-Thy-1.1 injection compared to chimeric rats without glomerular injury. The level of BM-derived endothelial cells remained high at day 28. We also observed a more than sevenfold increase in the number of BM-derived mesangial cells at day 28. BM-derived endothelial and mesangial cells were fully integrated in the glomerular structure. Our data show that BM-derived cells participate in glomerular endothelial and mesangial cell turnover and contribute to microvascular repair. These findings provide novel insights into the pathogenesis of renal disease and suggest a potential role for stem cell therapy.

Amelioration of anti-Thy1-glomerulonephritis by PPAR-γ agonism without increase of endothelial progenitor cell homing

“…Although we observed no significant differences in endothelial cell content between the groups, this may have been caused by a high variability in RECA-positive cell quantification, probably due to the irregular RECA staining pattern in the injured glomerulus. Thus this does not exclude a potential effect on endothelial cell proliferation or incorporation of bone marrow-derived endothelial cells, particularly since the number of bone marrow-derived cells in untreated nephritic rats is modest [3 cells per glomerular section in this study, which is in accordance with our laboratory's previous observations (21)]. Rosiglitazone is known to stimulate EPC function and differentiation in mice (31) and humans (19,31), which appears to be a drug class effect, as PPAR-␥ agonist pioglitazone has similar effects in mice (5) and humans (33).…”

“…Consistently, the limited upregulation of angiogenic factors in uninephrectomized rats injected with anti-Thy1.1 antibody is associated with a progressive course of the glomerulonephritis (30). Our laboratory has shown that glomerular endothelial repair after anti-Thy1-glomerulonephritis is in part dependent on bone marrow-derived EPC (21).…”

“…Rats were killed 7 days after injection with anti-Thy1, at which time point our laboratory has previously seen the highest number of incorporated bone marrow-derived endothelial cells (21). Double-staining with WagRij-specific anti-MHC I U9F4 antibody and endothelial-specific RECA antibody confirmed the presence of bone marrow-derived endothelial cells in the glomeruli (Fig.…”

14S,21R-dihydroxy-docosahexaenoic Acid Treatment Enhances Mesenchymal Stem Cell Amelioration of Renal Ischemia/Reperfusion Injury

“…However, the mechanisms by which MSCs ameliorate I/R injury are not clear. Several studies have demonstrated the capacity of MSC to differentiate into kidney cells [11][12][13][14]. Controversial studies indicated that the grafted MSCs were not the predominant cellular components involved in the regeneration of injured tubuli [7,59], and it has been postulated that, rather than differentiation, cell fusion accounts for these cells [7,[59][60][61].…”

“…In particular, MSCs can ameliorate renal ischemia/ reperfusion (I/R) injury [5][6][7][8][9][10]. It has been reported that MSCs repair renal damage by differentiating into tubular epithelial cells [11], mesangial cells [12], endothelial cells [13], and podocytes [14], and by producing renotrophic cytokines and growth factors [15][16][17][18][19]. For example, MSCs can produce insulin growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) [15], both of which are renal-protective or renotrophic factors [18,19].…”