( dozens of mice using both healthy and ...)Gene therapy converts dead bone graft to new, living tissue

dozens of mice, using both healthy and dead segments, then scanned the surrounding inflammatory tissue for differences in the levels of the active genes. He discovered that the genes that create two key proteins in living bone, called RANKL and VEGF, were barely expressed around the dead bone. He then modified a harmless virus to carry these genes, devised a method of freeze-drying a paste containing the virus so it could be easily handled, and painted it directly onto a bone graft during surgery.

Numerous tests in mice confirmed that the virus permeated the inflammatory tissue around the dead bone and turned on the genes. The mouse body then began to treat the implanted bone as if it were its own tissue instead of a foreign object, which would normally trigger the body to wrap the "invader" in scar tissue.

"That recognition is the key," says Schwarz. "It's at that point that the body actually begins changing the dead, foreign bone splint, into the body's own, whole, living bone."

Such a transformation can occur because mammals use their skeletons for both support and as a kind of "calcium bank." If calcium, which is necessary for such important functions as maintaining the brain and heart, runs low, cells called osteoclasts dig out the calcium from our bones. This is why doctors encourage post-menopausal women to take calcium supplements, so that the body doesn't raid their bones for the calcium it needs. The process works both ways, fortunately, as another set of cells, called osteoblasts, rebuilds the bone when the body has excess calcium. In an average year, a healthy person may remove and rebuild 10 percent of his or her bone structure.

This process of teardown and rebuilding is triggered in the dead bone when Schwarz paints it with the genetically modified virus. New blood vessels begin to grow around and into the bone splint, stripping it down in times when the body needs the calcium, and rebuilding it when calcium levels rise.
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Source:University of Rochester Medical Center

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