The coronary delivery of marrow stromal cells for myocardial regeneration:Pathophysiologic and therapeutic implications

Objectives: Bone marrow stromal cells contain "adult stern cells." We teste d the hypothesis that coronary-infused bone marrow stromal cells may popula te the infarcted heart and undergo milieu-dependent differentiation to rege nerate functional tissues with different phenotypic features. Methods: Isogenic adult rats were used as donors and recipients to simulate autologous transplantation clinically. Myocardial infarction was created b y proximal occlusion of left coronary artery in 12 recipient rats. Isolated bone marrow stromal cells were purified, expanded, and retrovirally transd uced with LacZ reporter gene for cell labeling. Stromal cells were then inf used into the briefly distally clamped ascending aorta of recipient rats 2 weeks after left coronary artery ligation. The hearts were harvested immedi ately (n = 2) or 4 weeks (n = 10) later to trace the implanted cells and id entify their phenotypes. Results: Viable cells labeled with LacZ reporter gene were identified in 8 recipient hearts. Immediately after cell infusion, the labeled cells were t rapped within the coronary capillaries. After 4 weeks, they could be detect ed individually or in clusters within myocardial scar expressing fibroblast ic phenotype or outside the infarction area with morphologic features of no rmal cardiomyocytes. Some were incorporated into endocardium and capillary endothelium. Conclusions: Our findings suggest that bone marrow stromal cells can traffi c through the coronary system to the injured heart and form cardiomyocytes or fibroblasts, depending on the specific microenvironment. Endothelial pro genitor cells in the stromal cell population may be involved in the postinf arction neovascularization process. Whether therapeutic use of bone marrow stromal cells can improve the myocardial healing and remodeling process aft er infarction is worthy of further investigation.