Abstract 3043: Circulating Mesenchymal Stem Cells Are Associated With Cardiac Allograft Vasculopathy
Cardiac allograft vasculopathy (CAV) remains a major complication limiting long term survival after heart transplantation (HTX). The pathogenesis of CAV is multifactorial and is mediated by immunological and non-immunological processes. Histologically, CAV is characterized by concentric intimal hyperplasia of the coronary arteries induced by infiltrating fibroblasts, lymphocytes, macrophages and vascular smooth muscle cells. Although the origin of these infiltrating cells is unclear, accumulating evidence suggests that bone marrow derived stem cells might play a role in chronic rejection. Furthermore, there is evidence that multipotent mesenchymal progenitors can be isolated from peripheral blood. Whether these cells can contribute to CAV pathogenesis is unclear. Peripheral blood samples of 50 HTX patients with 5 to 10 years follow up post transplant were collected. CAV was diagnosed in 25 patients by angiography. Circulating cells were isolated from the mononuclear cell fraction and cultured. Colony forming units (CFUs) were counted three weeks after initial plating and compared between patient groups. CFUs were stimulated to differentiate into mesenchymal lineages in vitro. Phenotyping of CFUs was performed by multiparametric flow cytometric analysis with fluorescence conjugated monoclonal antibodies. Flow cytometric analyses revealed that CFUs express the CD14, CD45 and CD34 antigens commonly found on monocyte-derived mesenchymal stem cells (MSCs). Multipotency of these cells was demonstrated by the capacity to differentiate into adipocytes, chondrocytes, and osteocytes in vitro. The number of circulating MSCs quantified by CFU determination was significantly higher in the CAV patient group (p<0.01). The results indicate that the number of circulating MSCs is associated with CAV pathogenesis. We hypothesize that MSCs could be involved in the intimal hyperplasia of coronary arteries in CAV patients. Antagonising MSC recruitment mechanisms could therefore be beneficial in controlling MSC infiltration to subsequently prevent CAV.