CD31+ cells represent highly angiogenic and vasculogenic cells in bone marrow: novel role of non-endothelial CD31+ cells in neovascularization and their therapeutic effects on ischemic vascular disease

• Type of Material: Article
• Authors: Hyongbum Kim, Emory University; Hyun-Jai Cho, Tufts University; Sung-Whan Kim, Emory University; Bianling Liu, Tufts University; Yong Jin Choi, Emory University; JiYoon Lee, Emory University; Young-Doug Sohn, Emory University; Min-Young Lee, Emory University; Mackenzie A. Houge, Emory University; Young Sup Yoon, Emory University
• Language: English
• Date: 2010-09-03
• Publisher: American Heart Association
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 American Heart Association, Inc.
• Final Published Version (URL): http://circres.ahajournals.org/content/107/5/602
• Title of Journal or Parent Work: Circulation Research
• ISSN: 0009-7330
• Volume: 107
• Issue: 5
• Start Page: 602
• End Page: 614
• Grant/Funding Information: National Heart, Lung, and Blood Institute : NHLBI; This work was supported in part by National Institutes of Health grants (HL079137, HL084471), a grant (SC4300) from the Stem Cell Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic ofKorea, Department of Defense Idea Grant, and an American Heart Association Postdoctoral Fellowship (H.K.).
• Keywords: Peripheral vascular disease; Bone marrow; Angiogenesis; Vasculogenesis; CD31 (PECAM-1)
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Cell

Abstract

Rationale Bone marrow (BM) cells play an important role in physiologic and therapeutic neovascularization. However, it remains unclear whether any specific uncultured BM cell populations have higher angiogenic and vasculogenic activities. Moreover, there has been controversy regarding the vasculogenic ability of BM cells. Objective Preliminary flow cytometric analysis showed that CD31, traditionally a marker for endothelial cells, is expressed in certain non-endothelial BM mononuclear cells (MNCs) in both human and mouse. Based on the conserved CD31 expression in the axis of hematopoietic stem/progenitor cells (HSC/HPCs) to endothelial cells, we further sought to determine the comprehensive vasculogenic and angiogenic characteristics of human and mouse BM-derived CD31+ cells. Methods and Results Flow cytometric analysis demonstrated that all CD31+ cells derived from BM were CD45+ and expressed markers for both HSC/HPCs and ECs. Comprehensive gene expression analyses revealed that BM-CD31+ cells expressed higher levels of angiogenic genes than CD31− cells. Endothelial progenitor cells, as well as HSC/HPCs, were almost exclusively confined to the CD31+ cell fraction, and culture of CD31+ cells under defined conditions gave rise to endothelial cells. Finally, injection of CD31+ cells into ischemic hindlimb repaired ischemia, increased expression of angiogenic and chemoattractive factors, and in part directly contributed to vasculogenesis, as demonstrated by both three-dimensional confocal microscopy and flow cytometry. Conclusions These data indicate that BM-CD31+ cells represent highly angiogenic and vasculogenic cells and can be a novel and highly promising source of cells for cell therapy to treat ischemic cardiovascular diseases.