Stem cell therapy with skeletal myoblasts accelerates neointima formation in a mouse model of vein graft disease

Abstract

Although still a matter of controversial discussion, skeletal myoblasts are one of the options for stem cell transplantation improving cardiac function after myocardial infarction, exhibiting several advantages including the availability, the ability of self-renewal and differentiation, and the lack of ethical and immunological problems. The aim of this study was to investigate the impact of stem cell therapy with skeletal myoblasts on experimental venous bypass grafts in a mouse model of vein graft disease. Forty C57BL/6J mice underwent bypass grafting interposing a venous bypass graft of the donor mouse into the carotid artery of the recipient mouse. Twenty mice received periadventitially treatment with 1 million fluorescence labeled skeletal myoblasts suspended in culture medium (treatment group), the other twenty mice received only culture medium without myoblasts (control group). Two weeks after bypass surgery, the vein grafts of all 40 mice were harvested, stained and histologically investigated under light and immunofluorescence microscope. Against our expectations, skeletal myoblasts stayed in place and were still located in the adventitia after bypass grafting. Additionally, vein grafts of the myoblast group revealed a 2fold increased neoneointima formation, a decreased media thickness, a slightly increased neovascularization, a higher percentage of reendothelialization and also a slightly higher percentage of PDGFR ɑ, PDGFR ß, MMP-7 and MMP-9 positive cells, suggesting a paracrine mechanism responsible for accelerated neointima formation. In conclusion, the results of our study do not support the use of skeletal myoblast for the treatment of vein graft disease after coronary artery bypass surgery.

Keywords: Coronary artery bypass grafting; Mouse model; Skeletal myoblasts; Stem cell therapy; Vein graft disease.