Cultured human bone marrow-derived CD31+ cells are effective for cardiac and vascular repair through enhanced angiogenic, adhesion, and anti-inflammatory effects

Sung Whan Kim, Mackenzie Houge, Milton Brown, Michael E. Davis, Youngsup Yoon

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background Cell therapy for cardiovascular disease has been limited by low engraftment of administered cellsand modest therapeutic effects. Bone marrow (BM) -derived CD31+ cells are a promising cell source owing to theirhigh angiovasculogenic and paracrine activities.

Results The CD31+ cells cultured in endothelial cell medium (EC-CD31+ cells) showed the highest adhesion andangiogenic activities and lowest inflammatory properties in vitro compared with uncultured or other cultured CD31+ cells.When implanted into mouse MI or HLI models, EC-CD31+ cells improved cardiac function and repaired limb ischemiato a greater extent than uncultured CD31+ cells. Histologically, injected EC-CD31+ cells exhibited higher retention,neovascularization, and cardiomyocyte proliferation. Importantly, cell retention and endothelial transdifferentiationwas sustained up to 1 year.

Objectives This study sought to identify culture conditions that could augment the cell adhesion, angiogenic, andanti-inflammatory activities of BM-derived CD31+ cells, and to determine whether these cultured CD31+ cells areeffective for cardiac and vascular repair.

Methods CD31+ cells were isolated from human BM by magnetic-activated cell sorting and cultured for 10 daysunder hematopoietic stem cell, mesenchymal stem cell, or endothelial cell culture conditions. These cells werecharacterized by adhesion, angiogenesis, and inflammatory assays. The best of the cultured cells were implantedinto myocardial infarction (MI) and hindlimb ischemia (HLI) models to determine therapeutic effects and underlyingmechanisms.

Conclusions Short-term cultured EC-CD31+ cells have higher cell engraftment, vessel-formation, cardiomyocyteproliferation, and anti-inflammatory potential, are highly effective for both cardiac and peripheral vascularrepair, and enhance survival of mice with heart failure. These cultured CD31+ cells may be a promising source fortreating ischemic cardiovascular diseases. (J Am Coll Cardiol 2014;64:168194)

Original languageEnglish
Pages (from-to)1681-1694
Number of pages14
JournalJournal of the American College of Cardiology
Volume64
Issue number16
DOIs
Publication statusPublished - 2014 Jan 1

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Blood Vessels
Anti-Inflammatory Agents
Bone Marrow
Cultured Cells
Endothelial Cells
Therapeutic Uses
Hindlimb
Cell Adhesion
Cardiovascular Diseases
Ischemia
Myocardial Infarction
Cell- and Tissue-Based Therapy
Hematopoietic Stem Cells
Mesenchymal Stromal Cells
Cardiac Myocytes
Extremities
Heart Failure
Cell Culture Techniques

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

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title = "Cultured human bone marrow-derived CD31+ cells are effective for cardiac and vascular repair through enhanced angiogenic, adhesion, and anti-inflammatory effects",
abstract = "Background Cell therapy for cardiovascular disease has been limited by low engraftment of administered cellsand modest therapeutic effects. Bone marrow (BM) -derived CD31+ cells are a promising cell source owing to theirhigh angiovasculogenic and paracrine activities.Results The CD31+ cells cultured in endothelial cell medium (EC-CD31+ cells) showed the highest adhesion andangiogenic activities and lowest inflammatory properties in vitro compared with uncultured or other cultured CD31+ cells.When implanted into mouse MI or HLI models, EC-CD31+ cells improved cardiac function and repaired limb ischemiato a greater extent than uncultured CD31+ cells. Histologically, injected EC-CD31+ cells exhibited higher retention,neovascularization, and cardiomyocyte proliferation. Importantly, cell retention and endothelial transdifferentiationwas sustained up to 1 year.Objectives This study sought to identify culture conditions that could augment the cell adhesion, angiogenic, andanti-inflammatory activities of BM-derived CD31+ cells, and to determine whether these cultured CD31+ cells areeffective for cardiac and vascular repair.Methods CD31+ cells were isolated from human BM by magnetic-activated cell sorting and cultured for 10 daysunder hematopoietic stem cell, mesenchymal stem cell, or endothelial cell culture conditions. These cells werecharacterized by adhesion, angiogenesis, and inflammatory assays. The best of the cultured cells were implantedinto myocardial infarction (MI) and hindlimb ischemia (HLI) models to determine therapeutic effects and underlyingmechanisms.Conclusions Short-term cultured EC-CD31+ cells have higher cell engraftment, vessel-formation, cardiomyocyteproliferation, and anti-inflammatory potential, are highly effective for both cardiac and peripheral vascularrepair, and enhance survival of mice with heart failure. These cultured CD31+ cells may be a promising source fortreating ischemic cardiovascular diseases. (J Am Coll Cardiol 2014;64:168194)",
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Cultured human bone marrow-derived CD31+ cells are effective for cardiac and vascular repair through enhanced angiogenic, adhesion, and anti-inflammatory effects. / Kim, Sung Whan; Houge, Mackenzie; Brown, Milton; Davis, Michael E.; Yoon, Youngsup.

In: Journal of the American College of Cardiology, Vol. 64, No. 16, 01.01.2014, p. 1681-1694.

Research output: Contribution to journalArticle

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T1 - Cultured human bone marrow-derived CD31+ cells are effective for cardiac and vascular repair through enhanced angiogenic, adhesion, and anti-inflammatory effects

AU - Kim, Sung Whan

AU - Houge, Mackenzie

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AU - Davis, Michael E.

AU - Yoon, Youngsup

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N2 - Background Cell therapy for cardiovascular disease has been limited by low engraftment of administered cellsand modest therapeutic effects. Bone marrow (BM) -derived CD31+ cells are a promising cell source owing to theirhigh angiovasculogenic and paracrine activities.Results The CD31+ cells cultured in endothelial cell medium (EC-CD31+ cells) showed the highest adhesion andangiogenic activities and lowest inflammatory properties in vitro compared with uncultured or other cultured CD31+ cells.When implanted into mouse MI or HLI models, EC-CD31+ cells improved cardiac function and repaired limb ischemiato a greater extent than uncultured CD31+ cells. Histologically, injected EC-CD31+ cells exhibited higher retention,neovascularization, and cardiomyocyte proliferation. Importantly, cell retention and endothelial transdifferentiationwas sustained up to 1 year.Objectives This study sought to identify culture conditions that could augment the cell adhesion, angiogenic, andanti-inflammatory activities of BM-derived CD31+ cells, and to determine whether these cultured CD31+ cells areeffective for cardiac and vascular repair.Methods CD31+ cells were isolated from human BM by magnetic-activated cell sorting and cultured for 10 daysunder hematopoietic stem cell, mesenchymal stem cell, or endothelial cell culture conditions. These cells werecharacterized by adhesion, angiogenesis, and inflammatory assays. The best of the cultured cells were implantedinto myocardial infarction (MI) and hindlimb ischemia (HLI) models to determine therapeutic effects and underlyingmechanisms.Conclusions Short-term cultured EC-CD31+ cells have higher cell engraftment, vessel-formation, cardiomyocyteproliferation, and anti-inflammatory potential, are highly effective for both cardiac and peripheral vascularrepair, and enhance survival of mice with heart failure. These cultured CD31+ cells may be a promising source fortreating ischemic cardiovascular diseases. (J Am Coll Cardiol 2014;64:168194)

AB - Background Cell therapy for cardiovascular disease has been limited by low engraftment of administered cellsand modest therapeutic effects. Bone marrow (BM) -derived CD31+ cells are a promising cell source owing to theirhigh angiovasculogenic and paracrine activities.Results The CD31+ cells cultured in endothelial cell medium (EC-CD31+ cells) showed the highest adhesion andangiogenic activities and lowest inflammatory properties in vitro compared with uncultured or other cultured CD31+ cells.When implanted into mouse MI or HLI models, EC-CD31+ cells improved cardiac function and repaired limb ischemiato a greater extent than uncultured CD31+ cells. Histologically, injected EC-CD31+ cells exhibited higher retention,neovascularization, and cardiomyocyte proliferation. Importantly, cell retention and endothelial transdifferentiationwas sustained up to 1 year.Objectives This study sought to identify culture conditions that could augment the cell adhesion, angiogenic, andanti-inflammatory activities of BM-derived CD31+ cells, and to determine whether these cultured CD31+ cells areeffective for cardiac and vascular repair.Methods CD31+ cells were isolated from human BM by magnetic-activated cell sorting and cultured for 10 daysunder hematopoietic stem cell, mesenchymal stem cell, or endothelial cell culture conditions. These cells werecharacterized by adhesion, angiogenesis, and inflammatory assays. The best of the cultured cells were implantedinto myocardial infarction (MI) and hindlimb ischemia (HLI) models to determine therapeutic effects and underlyingmechanisms.Conclusions Short-term cultured EC-CD31+ cells have higher cell engraftment, vessel-formation, cardiomyocyteproliferation, and anti-inflammatory potential, are highly effective for both cardiac and peripheral vascularrepair, and enhance survival of mice with heart failure. These cultured CD31+ cells may be a promising source fortreating ischemic cardiovascular diseases. (J Am Coll Cardiol 2014;64:168194)

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