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Neovascularization of ischemic myocardium by human bone-marrow–derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function

Nature Medicine volume 7, pages 430–436 (2001)Cite this article

Abstract

Left ventricular remodeling is a major cause of progressive heart failure and death after myocardial infarction. Although neoangiogenesis within the infarcted tissue is an integral component of the remodeling process, the capillary network is unable to support the greater demands of the hypertrophied myocardium, resulting in progressive loss of viable tissue, infarct extension and fibrous replacement. Here we show that bone marrow from adult humans contains endothelial precursors with phenotypic and functional characteristics of embryonic hemangioblasts, and that these can be used to directly induce new blood vessel formation in the infarct-bed (vasculogenesis) and proliferation of preexisting vasculature (angiogenesis) after experimental myocardial infarction. The neoangiogenesis resulted in decreased apoptosis of hypertrophied myocytes in the peri-infarct region, long-term salvage and survival of viable myocardium, reduction in collagen deposition and sustained improvement in cardiac function. The use of cytokine-mobilized autologous human bone-marrow–derived angioblasts for revascularization of infarcted myocardium (alone or in conjunction with currently used therapies) has the potential to significantly reduce morbidity and mortality associated with left ventricular remodeling.

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Figure 1: G-CSF mobilizes into the circulation a human bone-marrow–derived population which differentiates into endothelial cells.
Figure 2: Injection of G-CSF–mobilized human CD34+ cells into rats with acute myocardial infarction induces neoangiogenesis involving endothelium of both human and rat origin at 2 wk post-LAD ligation.
Figure 3: Injection of G-CSF–mobilized human CD34+ cells into rats with acute infarction improves myocardial function.
Figure 4: Representative echocardiographic examples of rats undergoing LAD ligation and subsequently receiving saline (control) or human CD34+ cells intravenously.
Figure 5: Neoangiogenesis and improvement in myocardial function is dependent on angioblast population within human CD34+/CD117Bright subset.
Figure 6: Neoangiogenesis accompanying injection of human CD34+ lineage cells protects hypertrophied myocardial cells against apoptosis.
Figure 7: Injection of G-CSF–mobilized human CD34+ cells into rats with acute infarction modifies the process of myocardial remodeling.

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Authors and Affiliations

  1. Department of Surgery, Columbia University, New York, New York, USA

    A.A. Kocher, M.D. Schuster, J. Wang, N.M. Edwards & S. Itescu

  2. Department of Medicine, Columbia University, New York, New York, USA

    S. Takuma, D. Burkhoff, S. Homma & S. Itescu

  3. Department of Pathology, Columbia University, New York, New York, USA

    M.J. Szabolcs

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Kocher, A., Schuster, M., Szabolcs, M. et al. Neovascularization of ischemic myocardium by human bone-marrow–derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 7, 430–436 (2001). https://doi.org/10.1038/86498

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