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

Abstract

Objectives: Bone marrow stromal cells contain "adult stem cells." We tested the hypothesis that coronary-infused bone marrow stromal cells may populate the infarcted heart and undergo milieu-dependent differentiation to regenerate 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 by proximal occlusion of left coronary artery in 12 recipient rats. Isolated bone marrow stromal cells were purified, expanded, and retrovirally transduced with LacZ reporter gene for cell labeling. Stromal cells were then infused into the briefly distally clamped ascending aorta of recipient rats 2 weeks after left coronary artery ligation. The hearts were harvested immediately (n = 2) or 4 weeks (n = 10) later to trace the implanted cells and identify their phenotypes.

Results: Viable cells labeled with LacZ reporter gene were identified in 8 recipient hearts. Immediately after cell infusion, the labeled cells were trapped within the coronary capillaries. After 4 weeks, they could be detected individually or in clusters within myocardial scar expressing fibroblastic phenotype or outside the infarction area with morphologic features of normal cardiomyocytes. Some were incorporated into endocardium and capillary endothelium.

Conclusions: Our findings suggest that bone marrow stromal cells can traffic through the coronary system to the injured heart and form cardiomyocytes or fibroblasts, depending on the specific microenvironment. Endothelial progenitor cells in the stromal cell population may be involved in the postinfarction neovascularization process. Whether therapeutic use of bone marrow stromal cells can improve the myocardial healing and remodeling process after infarction is worthy of further investigation.