Syngeneic Bone Marrow Cell Therapy Prevents Intimal Proliferation in Allogeneic Vascular Transplantation

Abstract

Transplant arteriosclerosis is characterized by intraluminal obstructive proliferation occurring in response to immune-mediated arterial wall injury. Cell therapy with vascular progenitor cells have been suggested to repair intimal lesions following endothelial injury. The aim of the current study was to assess the effects of autologous bone marrow cell direct transfer and of Fucan-mobilization bone marrow-derived progenitor cells on intimal thickening in vascular grafts. Aortic allografts were performed in Brown Norway (BN) and Lewis (LEW) rats. Cell therapy was performed by injection of two doses of 10 million LEW bone marrow mononuclear cells to recipient LEW following aortic grafting. Fucan, a low molecular weight sulfated polysaccharide (LMWF) was used to mobilize bone marrow-derived progenitor cells. Five groups of 10 rats included: untreated isografts (BN to BN), untreated allografts, and three allografted groups, respectively, treated by fucan therapy, cell therapy, or cell and fucan therapy. Aorta were studied by morphometric analysis at 30 d. In the absence of treatment, intimal thickening was greater in allograft than in isograft groups (299±50 versus 3.5±1.7 μm, P<0.001). Cell therapy alone, fucan therapy alone, and the combined treatment were shown to prevent intimal thickening in allografts (5.1±1.7, 6.1±2.3, 4.1±2.5, versus 299±50 μm respectively, P<0.001). In the three treated groups, the intimal lining was a single layer of endothelial cells expressing CD34 positive, endothelial nitric oxide synthase (eNOS) positive, and Ox3 specific-recipient monoclonal antibody positive. These results provide the proof of concept of recipient syngenic bone-marrow cell therapy for the prevention of chronic vasculopathy.