Nestin, an intermediate filament protein, is widely used as stem cell marker. Nestin has been shown to interact with other cytoskeleton proteins, suggesting a role in regulating cellular cytoskeletal structure. These studies examined renal nestin localization and developmental expression in mice. In developing kidney, anti-nestin antibody revealed strong immunoreactivity in vascular cleft of the S-shaped body and vascular tuft of capillary loop-stage glomerulus. The nestin-positive structures also were labeled by endothelial cell markers FLK1 and CD31 in immature glomeruli. Nestin was not detected in epithelial cells of immature glomeruli. In contrast, in mature glomerular, nestin immunoreactivity was observed only outside laminin-positive glomerular basement membrane, and co-localized with nephrin, consistent with podocyte nestin expression. In adult kidney, podocytes were the only cells that exhibited persistent nestin expression. Nestin was not detected in ureteric bud and its derivatives throughout renal development. Cell lineage studies, using a nestin promoter-driven Cre mouse and a ROSA26 reporter mouse, showed a strong ␤-galactosidase activity in intermediate mesoderm in an embryonic day 10 embryo and all of the structures except those that were derived from ureteric bud in embryonic kidney through adult kidney. These studies show that nestin is expressed in progenitors of glomerular endothelial cells and renal progenitors that are derived from metanephric mesenchyme. In the adult kidney, nestin expression is restricted to differentiated podocytes, suggesting that nestin could play an important role in maintaining the structural integrity of the podocytes.

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Accumulative evidence demonstrated that mesenchymal stem cell (MSC) engraftment could protect tissue injury from ischemia/reperfusion (I/R). Hepatocyte growth factor (HGF) has important roles in the cell and tissue repairment and regeneration. Here we investigated the enhanced effects of HGF-modified MSCs on I/R-induced acute lung injury. Rat bone marrow-derived MSCs were successfully transfected to express HGF. HGF modification did not affect the characteristics of MSCs, and increased MSC viability, and inhibit the proinflammatory phenotype of MSCs in the inflammatory condition. In the rat model of I/R-induced lung injury, MSC-HGF engraftment attenuated lung wet-to-dry weight ratio, enhanced PaO level and improved lung pathological injury, compared with MSC treatment. Moreover, the decreased acitivity of malondialdehyde, myeloperoxidase and tumor necrosis factor-α and increased superoxide dismutase content and interleukin-10 level were also observed in the MSC-HGF treatment, compared with the MSC group. Importantly, we found that HGF contributed to the survival of engrafted MSCs in the lung tissue through upregulation of Bcl-2 level and reduction of Caspase 3 activation. Thus our data show for the first time a clear beneficial effect of HGF gene modification on the survival of MSCs and enhanced improvement for I/R-induced lung injury.