The body's natural response to a wound--sending specialized cells to the transplant site to initiate the development of scar tissue--might be a major contributor to chronic kidney rejection following transplant.
This is the first demonstration that kidney rejection is actually caused by the recipient's own cells' normal reaction to a wound, rather than by the donor organ cells, said Paul Grimm, M.D., UCSD School of Medicine associate clinic professor of pediatric and the lead author of the study, which appears in the July 12 New England Journal of Medicine.
Grimm and colleagues at the University of Manitoba, Winnipeg, Canada and University of Pennsylvania, report that chronic kidney rejection appears to be caused by the organ recipient's own cells - specifically, the mesenchymal cells - traveling to the transplant site and colonizing the area, creating an environment in which the donor organ cannot survive. Scarring of an organ, which occurs during the post-surgical healing process, is actually quite damaging, constricting blood vessels leading to the organ and causing it to fail prematurely.
According to Grimm, the mesenchymal cells act as "wandering carpenters" circulating through the blood stream, constantly on the lookout for damaged tissue.
"Have hammer, will travel" is the motto of the cells, Grimm said, and their mission is to repair damaged areas. But sometimes these cells can harm rather than heal.
"We don't know why on some occasions the repair leads to perfect healing, but other times the repair is imperfect leading to the chronic scarring that is part of rejection," Grimm said.
Grimm and colleagues are hopeful of what developments could come from this finding, suggesting that it might be possible to mitigate or prevent kidney rejection by developing methods of blocking these scar-promoting cells.
For this study, the team analyzed tissue samples from 14 patients who had experienced kidney rejection. Through chromosomal tracking, the team determined that the cells causing scarring and rejection in each patient had actually migrated to the organ site through the recipient's blood stream.
"These findings open the door to a room of transplant medicine we've never seen before," Dr. Grimm said. "We can now possibly find ways to block these scar-causing cells by shutting down the signals that activate them in the first place."
This study was funded by the Baxter Extramural Grant Program of the National Institutes of Health (National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Allergy and Infectious Diseases), UCSD School of Medicine Department of Pediatrics, and the Children's Hospital of Winnipeg Research Foundation.
Collaborators with Dr. Grimm on the research include David N. Rush, M.D., Peter Nickerson, M.D., John Jeffery, M.D., Rachel M. McKenna, Ph.D, Elzbieta Stern, M.Sc., and James Gough, M.D., all from the University of Manitoba, Winnipeg, Canada; and Rashmin C. Savani, M.B., CH.B., from the University of Pennsylvania.
* Dr. Grimm is out of the country until July 18 but is available on a limited basis for interviews until then.
Journal
New England Journal of Medicine