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Donor versus Recipient: Neointimal Cell Origin in Allograft Vascular Disease

Robert S. Liwski

Paul Johnson

Jean-Francois Legare

Timothy D. G. Lee

Gregory M. Hirsch

The most common and intractable pathological presentation of chronic rejection in hearttransplants is allograft vasculopathy (AV) characterized by the formation of a diffuse, occlusiveintimal lesion. To date there is no effective treatment or prevention of this condition,owing in part to an incomplete understanding of the mechanism underlying AV. Ithas been recently demonstrated that the neointimal lesion cells originate from the recipient,and derive at least in part from marrow-derived mesenchymal precursors. Thisis in direct conflict with the previously held hypothesis that lesion cells are derived fromthe adjacent vascular media in response to immune injury. A better understanding of thisrejection process might provide new therapeutic strategies which more appropriatelyaddress the recruitment, proliferation, and differentiation of progenitor mesenchymal lesioncells derived from the recipient.

Key Words: transplantation • allograft vasculopathy • neointimal origin • heart transplants • rejection

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