Effects of Human Amniotic Fluid Stem Cells in a Model of Aorta Allograft Vasculopathy

Abstract

Chronic allograft vasculopathy (CAV) is an important cause of graft loss. Considering the immune-in flammatory events involved in the development of CAV, therapeutic approaches to target this process are of relevance. Human amniotic fluid derived stem cells (hAFSC), a class of fetal, pluripotent stem cells with intermediate characteristics between embryonic and adult stem cells display immunomodulatory properties. hAFSC express mesenchymal and embryonic markers, show high proliferation rates, but do not induce tumor formation and their use does not raise ethical issues. Thus, we sought to investigate the effect of hAFSC on CAV in a model of aorta transplantation. Orthotopic aorta transplantation was performed using Fisher (F344) rats as donors and Lewis rats as recipients. Rats were divided into 3 groups: syngeneic (SYNG), untreated F344 receiving aorta from F344 (n=8); allogeneic (ALLO), Lewis rats receiving allogeneic aorta from F344 (n=8); and ALLO+hAFSC, ALLO rats treated with hAFSC (106 cells) (n=8). Histological analysis and immunohistochemistry were performed 30 days post transplantation. ALLO developed a robust aortic neointimal formation, accompanied by a high number of ED1+ and CD43+ cells, and enhanced expression of α-SMA in theneointima. Treatment with hAFSC diminished neointimal thickness and induced a significant decrease of ED1+, CD43+ cells and α-SMA expression in the neointima. Comparative analyses in the differents groups PARAMETERS SYNG ALLO ALLO+hAFSC Neointima thickness (μm) 0±0 208.7±25.4* 180.7±23.7* ED-1+ (cells/mm2) 0±0 4.845±841* 1.100±276*, #CD43+ (cells/mm2) 0±0 4.064±563* 1.080±309*,#α-SMA (%) 0±0 25±6* 8±3*, #*p<0.05 vs. SYNG; #P<0.05 vs. ALLO These preliminary results showed that hAFSC suppressed inflammation and myofibroblast migration to the intima, which may contribute to ameliorate vascular changes in CAV.