Journal Article

Identification of a coronary vascular progenitor cell in the human heart

D'Alessandro, David A, Bardelli, Silvana, Lo Monaco, Francesco, Urbanek, Konrad, Kajstura, Jan, Zeiher, Andreas M, Michler, Robert E, Ojaimi, Caroline, Hosoda, Toru, Pepe, Martino, Gonzalez, Arantxa, Hintze, Thomas H, Anversa, Piero, Leri, Annarosa, D'Amario, Domenico, Dimmeler, Stefanie, Bearzi, Claudia, Qanud, Khaled, Rota, Marcello

2009

Overview

Primitive cells capable of generating small resistance arterioles and capillary structures in the injured myocardium have been identified repeatedly. However, these cells do not form large conductive coronary arteries that would have important implications in the management of the ischemic heart. In the current study, we determined whether the human heart possesses a class of progenitor cells that regulates the growth of endothelial cells (ECs) and smooth muscle cells (SMCs) and vasculogenesis. The expression of vascular endothelial growth-factor receptor 2 (KDR) was used, together with the stem cell antigen c-kit, to isolate and expand a resident coronary vascular progenitor cell (VPC) from human myocardial samples. Structurally, vascular niches composed of c-kit-KDR-positive VPCs were identified within the walls of coronary vessels. The VPCs were connected by gap junctions to ECs, SMCs, and fibroblasts that operate as supporting cells. In vitro, VPCs were self-renewing and clonogenic and differentiated predominantly into ECs and SMCs and partly into cardiomyocytes. To establish the functional import of VPCs, a critical stenosis was created in immunosuppressed dogs, and tagged human VPCs were injected in proximity to the constricted artery. One month later, there was an increase in coronary blood flow (CBF) distal to the stenotic artery, resulting in functional improvement of the ischemic myocardium. Regenerated large, intermediate, and small human coronary arteries and capillaries were found. In conclusion, the human heart contains a pool of VPCs that can be implemented clinically to form functionally competent coronary vessels and improve CBF in patients with ischemic cardiomyopathy.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Actins - metabolism / Adult Stem Cells - cytology / Adult Stem Cells - physiology / Adult Stem Cells - transplantation / Animals / Antigens / arterioles / Biological Sciences / blood flow / Blood vessels / cardiomyocytes / cardiomyopathy / Cell Differentiation / Cell Proliferation / Cell Separation / Connexin 43 - metabolism / Coronary Circulation / Coronary Stenosis - pathology / Coronary Stenosis - physiopathology / Coronary Stenosis - therapy / Coronary vessels / Coronary Vessels - cytology / Coronary Vessels - physiopathology / Dogs / Endothelial cells / Endothelial Cells - cytology / Endothelial Cells - physiology / fibroblasts / gap junctions / Gene Expression Profiling / Genes / Heart / Heart attacks / Humans / Left coronary artery / Mast cells / Myocardial Ischemia - pathology / Myocardial Ischemia - physiopathology / Myocardial Ischemia - therapy / Myocardium / Myocytes, Cardiac - cytology / Myocytes, Cardiac - physiology / Myocytes, Smooth Muscle - cytology / Myocytes, Smooth Muscle - physiology / patients / Progenitor cells / Proto-Oncogene Proteins c-kit - metabolism / Regeneration - genetics / Regeneration - physiology / smooth muscle / Stem cells / Studies / Transplantation, Heterologous / Vascular Endothelial Growth Factor Receptor-2 - metabolism