Identification of a coronary vascular progenitor cell in the human heart
Authors: Andreas M Zeiher
Thomas H Hintze
Stefanie Dimmeler
David A D&#x27;Alessandro
Domenico D&#x27;Amario
Konrad Urbanek
Annarosa Leri
Arantxa Gonzalez
Toru Hosoda
Caroline Ojaimi
Silvana Bardelli
Francesco Lo Monaco
Claudia Bearzi
Jan Kajstura
Martino Pepe
Khaled Qanud
Robert E Michler
Marcello Rota
Piero Anversa
Journal: Proceedings of the National Academy of Sciences of the United States of America (2009)
Discipline: Multidisciplinary
Keywords: Primitive cells; resistance arterioles; capillary structures; injured myocardium; conductive coronary arteries
Affiliations: Department of Anesthesia and Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

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. 

Retracted: Yes

PubPeer comments:
 2019 retraction. https: www.pnas.org content early 2019 09 25 1916177116 The editors wish to note that, based on the recommendation of Harvard Medical School (HMS) and Brigham and Womanu2019s Hospital (BWH), we are retracting this paper. The HMS and BWH review of images contained in publications from the P.A. laboratory suggests that image data appeared to be modified in ways determined to fall outside acceptable image adjustment practices. The HMS BWH found instances of the following: Fig. 1A (Top Left) appears to have areas of c-kit-positive staining selectively inserted into the image plane; Fig. 1A (Bottom Left) appears to have areas of c-kit-positive staining selectively added, as well as the translocation of cells within the image. , 
 https: retractionwatch.com 2019 10 03 drip-drip-former-harvard-stem-cell-researcher-up-to-18-retractions ,