Identification of a coronary vascular progenitor cell in the human heart

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

Research output: Contribution to journalArticle

162 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)15885-15890
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number37
DOIs
StatePublished - Sep 15 2009

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Blood Vessels
Stem Cells
Coronary Vessels
Smooth Muscle Myocytes
Endothelial Cells
Myocardium
Capillary Resistance
Arteries
Vascular Endothelial Growth Factor Receptor-2
Gap Junctions
Arterioles
Cardiomyopathies
Cardiac Myocytes
Pathologic Constriction
Fibroblasts
Dogs
Antigens
Growth

ASJC Scopus subject areas

  • General

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Identification of a coronary vascular progenitor cell in the human heart. / Bearzi, Claudia; Leri, Annarosa; Lo Monaco, Francesco; Rota, Marcello; Gonzalez, Arantxa; Hosoda, Toru; Pepe, Martino; Qanud, Khaled; Ojaimi, Caroline; Bardelli, Silvana; D'Amario, Domenico; D'Alessandro, David A.; Michler, Robert E.; Dimmeler, Stefanie; Zeiher, Andreas M.; Urbanek, Konrad; Hintze, Thomas H.; Kajstura, Jan; Anversa, Piero.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 37, 15.09.2009, p. 15885-15890.

Research output: Contribution to journalArticle

Bearzi, C, Leri, A, Lo Monaco, F, Rota, M, Gonzalez, A, Hosoda, T, Pepe, M, Qanud, K, Ojaimi, C, Bardelli, S, D'Amario, D, D'Alessandro, DA, Michler, RE, Dimmeler, S, Zeiher, AM, Urbanek, K, Hintze, TH, Kajstura, J & Anversa, P 2009, 'Identification of a coronary vascular progenitor cell in the human heart', Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 37, pp. 15885-15890. https://doi.org/10.1073/pnas.0907622106
Bearzi, Claudia ; Leri, Annarosa ; Lo Monaco, Francesco ; Rota, Marcello ; Gonzalez, Arantxa ; Hosoda, Toru ; Pepe, Martino ; Qanud, Khaled ; Ojaimi, Caroline ; Bardelli, Silvana ; D'Amario, Domenico ; D'Alessandro, David A. ; Michler, Robert E. ; Dimmeler, Stefanie ; Zeiher, Andreas M. ; Urbanek, Konrad ; Hintze, Thomas H. ; Kajstura, Jan ; Anversa, Piero. / Identification of a coronary vascular progenitor cell in the human heart. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 37. pp. 15885-15890.
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T1 - Identification of a coronary vascular progenitor cell in the human heart

AU - Bearzi, Claudia

AU - Leri, Annarosa

AU - Lo Monaco, Francesco

AU - Rota, Marcello

AU - Gonzalez, Arantxa

AU - Hosoda, Toru

AU - Pepe, Martino

AU - Qanud, Khaled

AU - Ojaimi, Caroline

AU - Bardelli, Silvana

AU - D'Amario, Domenico

AU - D'Alessandro, David A.

AU - Michler, Robert E.

AU - Dimmeler, Stefanie

AU - Zeiher, Andreas M.

AU - Urbanek, Konrad

AU - Hintze, Thomas H.

AU - Kajstura, Jan

AU - Anversa, Piero

PY - 2009/9/15

Y1 - 2009/9/15

N2 - 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.

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