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Previous Volume 345:93-97 July 12, 2001 Number 2 Next

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ABSTRACT

Background Tissue remodeling depends on mesenchymal cells (fibroblasts and myofibroblasts) and is a prominent feature of chronic renal-transplant rejection. It is not known whether the mesenchymal cells that participate in remodeling originate locally or from circulating precursor cells.

Methods We obtained biopsy specimens of renal allografts from six male recipients of an allograft from a female donor, four female recipients of an allograft from a male donor, two male recipients of an allograft from a male donor, and two female recipients of an allograft from a female donor. All the allografts were undergoing chronic rejection. We used immunohistochemical methods to identify mesenchymal cells with smooth-muscle -actin and in situ hybridization to identify mesenchymal cells with Y-chromosome DNA.

Results No Y-chromosome bodies were identified in the case of the two renal-allograft specimens in which both the donor and the recipient were female. In the case of the two renal-allograft specimens in which both the donor and the recipient were male, approximately 40 percent of mesenchymal cells contained a Y-chromosome body. In the case of the six specimens in which the donor was female and the recipient was male, a mean (±SD) of 34±16 percent of mesenchymal cells in the neointima, 38±12 percent of such cells in the adventitia, and 30±7 percent of such cells in the interstitium contained the Y-chromosomal marker, indicating that they originated from the recipient rather than the donor. In the case of the four renal-allograft specimens in which the donor was male and the recipient was female, the respective values were 24±15 percent, 33±9 percent, and 23±8 percent, indicating a persistent population of donor mesenchymal cells.

Conclusions The presence of mesenchymal cells of host origin in the vascular and interstitial compartments of renal allografts undergoing chronic rejection provides evidence that a circulating mesenchymal precursor cell has the potential to migrate to areas of inflammation.

Source Information

From the Department of Pediatrics, University of California at San Diego, San Diego (P.C.G.); the Departments of Internal Medicine (P.N., J.J., R.M.M., E.S., D.N.R.) and Pathology (J.G.), University of Manitoba, Winnipeg, Canada; and the Department of Pediatrics, University of Pennsylvania, Philadelphia (R.C.S.).

Address reprint requests to Dr. Grimm at the Department of Pediatrics, UCSD, 9500 Gilman Dr., MC 0831, La Jolla, CA 92093-0831, or at pgrimm{at}ucsd.edu.

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