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, Young Sup Yoon

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48 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1681-1694
Number of pages14
JournalJournal of the American College of Cardiology
Issue number16
Publication statusPublished - 2014 Oct 21

Bibliographical note

Funding Information:
This work was supported in part by NIH grants DP3DK094346 , UL1 RR025008 , and NIH contract HHSN268201000043C; by NSF-EBICS grant, CBET-0939511 to Dr. Yoon; and by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MOE) (No. NRF-2013R1A1A2059998), and Korean government (MSIP, 2013 041811) to Dr. Kim. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Publisher Copyright:
© 2014 American College of Cardiology Foundation.

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine


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