CD31 + cells represent highly angiogenic and vasculogenic cells in bone marrow: Novel role of nonendothelial CD31 + cells in neovascularization and their therapeutic effects on ischemic vascular disease

Hyongbum Kim, Hyun Jai Cho, Sung Whan Kim, Bianling Liu, Yong Jin Choi, Jiyoon Lee, Young Doug Sohn, Min Young Lee, MacKenzie A. Houge, Young Sup Yoon

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Rationale: Bone marrow (BM) cells play an important role in physiological 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 nonendothelial BM mononuclear cells 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 endothelial cells. 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 3D 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.

Original languageEnglish
Pages (from-to)602-614
Number of pages13
JournalCirculation Research
Volume107
Issue number5
DOIs
Publication statusPublished - 2010 Sep 3

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Therapeutic Uses
Vascular Diseases
Bone Marrow Cells
Endothelial Cells
Hematopoietic Stem Cells
Physiologic Neovascularization
Angiogenesis Inducing Agents
Hindlimb
Cell- and Tissue-Based Therapy
Confocal Microscopy
Flow Cytometry
Cardiovascular Diseases
Ischemia
Cell Culture Techniques
Bone Marrow
Gene Expression
Injections
Population
Genes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Kim, Hyongbum ; Cho, Hyun Jai ; Kim, Sung Whan ; Liu, Bianling ; Choi, Yong Jin ; Lee, Jiyoon ; Sohn, Young Doug ; Lee, Min Young ; Houge, MacKenzie A. ; Yoon, Young Sup. / CD31 + cells represent highly angiogenic and vasculogenic cells in bone marrow : Novel role of nonendothelial CD31 + cells in neovascularization and their therapeutic effects on ischemic vascular disease. In: Circulation Research. 2010 ; Vol. 107, No. 5. pp. 602-614.
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abstract = "Rationale: Bone marrow (BM) cells play an important role in physiological 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 nonendothelial BM mononuclear cells 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 endothelial cells. 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 3D 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.",
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CD31 + cells represent highly angiogenic and vasculogenic cells in bone marrow : Novel role of nonendothelial CD31 + cells in neovascularization and their therapeutic effects on ischemic vascular disease. / Kim, Hyongbum; Cho, Hyun Jai; Kim, Sung Whan; Liu, Bianling; Choi, Yong Jin; Lee, Jiyoon; Sohn, Young Doug; Lee, Min Young; Houge, MacKenzie A.; Yoon, Young Sup.

In: Circulation Research, Vol. 107, No. 5, 03.09.2010, p. 602-614.

Research output: Contribution to journalArticle

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T1 - CD31 + cells represent highly angiogenic and vasculogenic cells in bone marrow

T2 - Novel role of nonendothelial CD31 + cells in neovascularization and their therapeutic effects on ischemic vascular disease

AU - Kim, Hyongbum

AU - Cho, Hyun Jai

AU - Kim, Sung Whan

AU - Liu, Bianling

AU - Choi, Yong Jin

AU - Lee, Jiyoon

AU - Sohn, Young Doug

AU - Lee, Min Young

AU - Houge, MacKenzie A.

AU - Yoon, Young Sup

PY - 2010/9/3

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N2 - Rationale: Bone marrow (BM) cells play an important role in physiological 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 nonendothelial BM mononuclear cells 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 endothelial cells. 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 3D 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.

AB - Rationale: Bone marrow (BM) cells play an important role in physiological 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 nonendothelial BM mononuclear cells 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 endothelial cells. 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 3D 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.

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