Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia

OBJECTIVES We tested the hypothesis that intramyocardial injection of autol ogous bone marrow (ABM) promotes collateral development in ischemic porcine myocardium. We also defined, in vitro, whether bone marrow (BM) cells secr ete vascular endothelial growth factor (VEGF) and macrophage chemoattractan t protein-1 (MCP-1). BACKGROUND The natural processes leading to collateral development are extr emely complex, requiring multiple growth factors interacting in concert and in sequence. Because optimal angiogenesis may therefore, require multiple angiogenic factors, we thought that injection of BM, which contains cells t hat secrete numerous angiogenic factors, might provide optimal therapeutic angiogenesis, METHODS Bone marrow was cultured four weeks in vitro. Conditioned medium wa s assayed for VEGF and MCP-1 and was added to cultured pig aortic endotheli al cells (PAEC) to assess proliferation. Four weeks after left circumflex a meroid implantation, freshly aspirated ABM (n = 7) or heparinized saline (n = 7) was injected transendocardially into the ischemic zone (0.2 ml/inject ion at 12 sites). Echocardiography to assess myocardial thickening and micr ospheres to assess perfusion were performed at rest and during stress. RESULTS Vascular endothelial growth factor and MCP-1 concentrations increas ed in a time-related manner. The conditioned medium enhanced, in a dose rel ated manner, PAEC proliferation. Collateral flow (ischemic/normal zone X 10 0 improved in ABM-treated pigs (ABM: 98 +/- 14 vs. 83 +/- 12 at rest, p = 0 .001; 89 +/- 18 vs. 78 +/- 12 during adenosine, p = 0.025; controls: 92 +/- 10 vs. 89 +/- 9 at rest, p = 0.49; 78 +/- 11 vs.77 +/- 5 during adenosine, p = 0.75). Similarly, contractility increased in ABM-treated pigs (ABM: 83 +/- 21 vs, 60 +/- 32 at rest, p = 0.04; 91 +/- 44 vs. 36 +/- 43 during pac ing, p = 0.056; controls: 69 +/- 48 vs. 64 +/- 46 at rest, p = 0.74; 65 +/- 56 vs. 37 +/- 56 during pacing, p = 0.23). CONCLUSIONS Bone marrow cells secrete angiogenic factors that induce endoth elial cell proliferation and, when injected transendocardially, augment col lateral perfusion and myocardial function in ischemic myocardium. (J Am Coi l Cardiol 2001;37:1726-32) (C) 2001 by the American College of Cardiology.