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Stem cells bring fast direct improvement, without differentiation, in acute renal failure

rs Medical Center; Jorge Isaac, University of Utah; and Claudia Lange, Bone Marrow Transplantation Center, Hamburg.

Stem cell time in the kidney: about two hours

At first, Westenfelder conceded, the researchers experienced "substantial frustration because the cells were detectable in the kidney for only two hours and then 'disappeared.' But after entry into the kidneys with ARF, we found that they fundamentally changed a number of important gene expression profiles. In fact, the intrarenal location of administered stem cells is such that it facilitates the delivery of renoprotective growth factors and cytokines to the sites where kidney cells are primarily destroyed from both the blood and urinary aspects of the cells that must be protected and repaired!" Westenfelder reported.

With their rapid mode of action within only two hours in the kidney, the researchers deduced that the mechanism mediating the protective effects of MSC (mesenchymal stem cells) "must be primarily paracrine, as implied by their demonstrated expression of several growth factors such as HGF (hepatocyte growth factor), VEGF and IGF-1, all known to improve renal function in ARF, mediated by their antiapoptotic, mitogenic and other cytokine actions," the paper said.

"Specifically, these as yet incompletely defined paracrine actions of MSC result in the renal downregulation of proinflammatory cytokines IL-1-beta, TNF-alpha, and IFN-gamma, as well as iNOS (inducible nitric oxide synthase), and upregulation of anti-inflammatory and organ-protective interleukin-10, as well as bFGF (basic fibroblast growth factor), TGF-alpha (transforming growth factor alpha) and antiapoptotic Bc1-2," the paper added.

Beneficial paracrine actions are elicited early and late after onset of ARF

The study said it "provides the first clear evidence that therapy with MSC affords significant renoprotection in rats with ischemic/reperfusion (I/R) ARF. Animals in
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15-Aug-2005


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