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Text
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<a href="http://doi.org/10.1161/CIRCRESAHA.111.250126" target="_blank" rel="noreferrer noopener">http://doi.org/10.1161/CIRCRESAHA.111.250126</a>
Pages
241–252
Issue
2
Volume
110
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Title
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Induction of vascular progenitor cells from endothelial cells stimulates coronary collateral growth.
Publisher
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Circulation research
Date
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2012
2012-01
Subject
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*Collateral Circulation; *Coronary Circulation; Animal; Animals; Biomarkers/metabolism; Cell Differentiation; Cell Lineage; Cells; Coronary Occlusion/genetics/metabolism/pathology/physiopathology/*surgery; Coronary Vessels/metabolism/pathology/*physiopathology; Cultured; Developmental; Disease Models; Endothelial Cells/metabolism/pathology/*transplantation; Epigenesis; Gene Expression Profiling; Gene Expression Regulation; Genetic; Induced Pluripotent Stem Cells/metabolism/*transplantation; Mice; Muscle; Myocytes; Neovascularization; Physiologic; Rats; Regenerative Medicine/methods; Regional Blood Flow; Reverse Transcriptase Polymerase Chain Reaction; SCID; Smooth; Smooth Muscle/metabolism/pathology/*transplantation; Sprague-Dawley; Teratoma/metabolism/pathology; Time Factors; Transcription Factors/genetics/metabolism; Transduction; Vascular/metabolism/pathology/*physiopathology
Creator
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Yin Liya; Ohanyan Vahagn; Pung Yuh Fen; Delucia Angelo; Bailey Erin; Enrick Molly; Stevanov Kelly; Kolz Christopher L; Guarini Giacinta; Chilian William M
Description
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RATIONALE: A well-developed coronary collateral circulation improves the morbidity and mortality of patients following an acute coronary occlusion. Although regenerative medicine has great potential in stimulating vascular growth in the heart, to date there have been mixed results, and the ideal cell type for this therapy has not been resolved. OBJECTIVE: To generate induced vascular progenitor cells (iVPCs) from endothelial cells, which can differentiate into vascular smooth muscle cells (VSMCs) or endothelial cells (ECs), and test their capability to stimulate coronary collateral growth. METHODS AND RESULTS: We reprogrammed rat ECs with the transcription factors Oct4, Klf4, Sox2, and c-Myc. A population of reprogrammed cells was derived that expressed pluripotent markers Oct4, SSEA-1, Rex1, and AP and hemangioblast markers CD133, Flk1, and c-kit. These cells were designated iVPCs because they remained committed to vascular lineage and could differentiate into vascular ECs and VSMCs in vitro. The iVPCs demonstrated better in vitro angiogenic potential (tube network on 2-dimensional culture, tube formation in growth factor reduced Matrigel) than native ECs. The risk of teratoma formation in iVPCs is also reduced in comparison with fully reprogrammed induced pluripotent stem cells (iPSCs). When iVPCs were implanted into myocardium, they engrafted into blood vessels and increased coronary collateral flow (microspheres) and improved cardiac function (echocardiography) better than iPSCs, mesenchymal stem cells, native ECs, and sham treatments. CONCLUSIONS: We conclude that iVPCs, generated by partially reprogramming ECs, are an ideal cell type for cell-based therapy designed to stimulate coronary collateral growth.
Identifier
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<a href="http://doi.org/10.1161/CIRCRESAHA.111.250126" target="_blank" rel="noreferrer noopener">10.1161/CIRCRESAHA.111.250126</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Collateral Circulation
*Coronary Circulation
2012
Animal
Animals
Bailey Erin
Biomarkers/metabolism
Cell Differentiation
Cell Lineage
Cells
Chilian William M
Circulation research
Coronary Occlusion/genetics/metabolism/pathology/physiopathology/*surgery
Coronary Vessels/metabolism/pathology/*physiopathology
Cultured
Delucia Angelo
Department of Integrative Medical Sciences
Developmental
Disease Models
Endothelial Cells/metabolism/pathology/*transplantation
Enrick Molly
Epigenesis
Gene Expression Profiling
Gene Expression Regulation
Genetic
Guarini Giacinta
Induced Pluripotent Stem Cells/metabolism/*transplantation
Kolz Christopher L
Mice
Muscle
Myocytes
NEOMED College of Medicine
Neovascularization
Ohanyan Vahagn
Physiologic
Pung Yuh Fen
Rats
Regenerative Medicine/methods
Regional Blood Flow
Reverse Transcriptase Polymerase Chain Reaction
SCID
Smooth
Smooth Muscle/metabolism/pathology/*transplantation
Sprague-Dawley
Stevanov Kelly
Teratoma/metabolism/pathology
Time Factors
Transcription Factors/genetics/metabolism
Transduction
Vascular/metabolism/pathology/*physiopathology
Yin Liya