Donor versus recipient: Neointimal cell origin in allograft vascular disease

The most common and intractable pathological presentation of chronic rejection in heart transplants is allograft vasculopathy (AV) characterized by the formation of a diffuse, occlusive intimal 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. It has been recently demonstrated that the neointimal lesion cells originate from the recipient, and derive at least in part from marrow-derived mesenchymal precursors. This is in direct conflict with the previously held hypothesis that lesion cells are derived from the adjacent vascular media in response to immune injury. A better understanding of this rejection process might provide new therapeutic strategies which more appropriately address the recruitment, proliferation, and differentiation of progenitor mesenchymal lesion cells derived from the recipient.