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

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)