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Updated: Jun 20, 2026
In Vitro Model of Coronary Angiogenesis
Published on: March 10, 2020
Identification of a coronary vascular progenitor cell in the human heart
Claudia Bearzi1, Annarosa Leri, Francesco Lo Monaco
1Department of Anesthesia and Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Insights
Human heart progenitor cells can regenerate damaged coronary arteries, improving blood flow in ischemic cardiomyopathy. These vascular progenitor cells (VPCs) offer a promising clinical approach for heart repair.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Stem Cell Research
Background:
- Primitive myocardial cells generate small vessels but not large coronary arteries in injured hearts.
- The potential for resident cardiac progenitor cells to form functional coronary arteries remains unexplored.
Purpose of the Study:
- To determine if the human heart harbors progenitor cells regulating endothelial cells (ECs), smooth muscle cells (SMCs), and vasculogenesis.
- To investigate the therapeutic potential of these cells in ischemic heart disease.
Main Methods:
- Isolated and expanded vascular progenitor cells (VPCs) from human myocardium using c-kit and vascular endothelial growth-factor receptor 2 (KDR) markers.
- Characterized VPCs in vitro for self-renewal, differentiation, and functional integration.
- Injected tagged human VPCs into dogs with induced coronary artery stenosis to assess in vivo efficacy.
Main Results:
- Identified c-kit-KDR-positive VPCs in vascular niches within coronary vessel walls, connected to supporting cells via gap junctions.
- Demonstrated in vitro self-renewal and differentiation of VPCs into ECs, SMCs, and cardiomyocytes.
- Showed in vivo regeneration of large, intermediate, and small coronary arteries and capillaries post-VPC injection, leading to increased coronary blood flow and improved myocardial function.
Conclusions:
- The human heart possesses a pool of vascular progenitor cells (VPCs) capable of forming functionally competent coronary vessels.
- Clinical implementation of these VPCs can improve coronary blood flow and treat ischemic cardiomyopathy.
Abstract:
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.
