Effects of Cell Grafting on Coronary Remodeling After Myocardial Infarction

BACKGROUND With recent advances in therapeutic applications of stem cells, cell engraftment has become a promising therapy for replacing injured myocardium after infarction. The survival and function of injected cells, however, will depend on the efficient vascularization of the new tissue. Here we describe the arteriogenic remodeling of the coronary vessels that supports vascularization of engrafted tissue postmyocardial infarction (post-MI). METHODS AND RESULTS Following MI, murine hearts were injected with a skeletal myoblast cell line previously shown to develop into large grafts. Microcomputed tomography at 28 days postengraftment revealed the 3-dimensional structure of the newly formed conducting vessels. The grafts elicited both an angiogenic response and arteriogenic remodeling of the coronary arteries to perfuse the graft. The coronaries upstream of the graft also remodeled, showing an increase in branching, and a decrease in vascular density. Histological analysis revealed the presence of capillaries as well as larger vascular lumens within the graft. Some graft vessels were encoated by smooth muscle α-actin positive cells, implying that vascular remodeling occurs at both the conducting arterial and microvascular levels. CONCLUSIONS Following MI and skeletal myoblast engraftment, the murine coronary vessels exhibit plasticity that enables both arteriogenic remodeling of the preexisting small branches of the coronary arteries and development of large and small smooth muscle encoated vessels within the graft. Understanding the molecular mechanisms underlying these 2 processes suggests mechanisms to enhance the therapeutic vascularization in patients with myocardial ischemia.