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MSCs and Kidney Diseases

There are a lot of reports that show the MSCs can repopulate the damaged kidney with varying degrees of significance. Intraparenchymal injection of bone marrow derived MSCs reduces kidney fibrosis after ischemic-reperfusion in cyclosporine-immunosuppressed rats. Initial experimental studies reported that the exogenous administration of MSCs to mice with acute renal injury could promote both structural and functional renal repair via the trandifferentiation of MSCs into tubular epithelium. However, only 2 to 2.5% of the injected MSCs showed engraftment.

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MSCs by virtue of their tropism for damaged kidneys and their ability to provide a local pro-survival environment may represent a useful strategy to preserve podocyte viability and reduce glomerular inflammation and sclerosis. A study in female mice that received a male bone marrow transplant for tubular injury showed about 4% of tubular cells to be positive for Y-chromosome which suggested that a small but significant amount of engrafted bone marrow derived cells participated in kidney regeneration. In contrast to this, other studies reported that arterial injection of MSCs reduced the necrosis, improved kidney function, and increased the proliferation of mesangial cells and their expression of α-smooth muscle actin (α-SMA), yet no incorporation of MSCs in to kidney structures was seen. These reports demonstrate that the direct engraftment of exogenously administered, and transdifferentiating MSCs is not the predominant mechanism in which MSCs enhance renal repair.

There is increasing evidence that mesenchymal stem cells can elicit kidney repair through paracrine and/or endocrine mechanisms, where they release trophic growth factors that modulate the immune response and consequently mediate repair. The ability of mesenchymal stem cells to inhibit the release of pro-inflammatory cytokines and secrete a variety of trophic growth factors that promote angiogenesis, mitogenesis, and proliferation whilst reducing apoptosis may collectively mediate the protective and regenerative effects in the kidneys of laboratory rodents.

A recent study of targeted delivery of bone marrow derived MSCs challenged this belief. In this study, researchers not only showed homing of bone marrow derived mesenchymal stem cells but also showed the recovery of kidneys in rat models of acute kidney injury. In a pilot clinical study of chronic kidney disease, two intravenous transplantations of ~1 million/MSCs/kg body showed significant difference between each of serum creatinine and creatinine clearance levels before and after MSC injection at 1, 3 and 6 months after infusion.