Bone Abstracts

Deceased donor kidneys are exposed to cold ischemic insult, which makes them particularly susceptible to the effects of cold ischemic injury during hypothermic preservation resulting in high rates of delayed graft function. Although cold storage reduces cellular oxygen demand, ischemia causes the rapid depletion of adenosine triphosphate and accumulation of toxic substances leading to cell death. BMP-7 is a valuable reagent in a field of tissue regeneration and preservation under ischemic conditions. Following these insights, we investigated the effect of rhBMP-7 on graft preservation during cold ischemia.

The study was conducted on experimental model of kidney cold ischemia in rats. Kidneys were perfused with saline, University of Wisconsin (UW), rhBMP-7 or rhBMP-7+ UW and exposed to cold ischemia for 6, 12 and 24 hours. Using PCR method the expression of mRNA BMP-7, TGF-β1, Smad1, Smad2, Smad3, Smad5 and Smad8 was analyzed. Immunohistochemical analysis was used to show expression and localization of BMP-7, TGF-β1, E-cadherin and α-SMA.

In tubular epithelial cells of the kidneys perfused with rhBMP-7 and rhBMP-7+UW solution the expression of BMP-7 and E-cadherin was observed after 24 hours of cold ischemia. In the kidneys not perfused with rhBMP-7 high expression of TGF-β1 and α-SMA was found. Also, in the kidneys perfused with rhBMP-7 solution level of mRNA BMP-7 expression was increased. In the same tissue higher level of mRNA Smad1, Smad5 and Smad8 expression, molecules of intracellular BMP-7 signal pathway, was proved. The levels of mRNA BMP-7, Smad1, Smad5 and Smad8 expression were equally present during whole time of cold ischemia.

BMP-7 maintains the morphology of the kidney tissue better than UW solution during 24 hours of cold ischemia. BMP-7 prevents epithelial to mesenchymal transformation and consequently maintains epithelial phenotype of tubular cells.