title: Bone marrow-derived CMPs and GMPs represent highly functional proangiogenic cells: implications for ischemic cardiovascular disease.
abstract: Clinical studies using bone marrow-derived proangiogenic cells (PACs) have demonstrated modest improvements of function and/or perfusion of ischemic myocardium or skeletal muscle. Because the identities of these PACs and their functional ability to promote neovascularization remain poorly understood, it is possible that a subset of robust PACs exists but is obscured by the heterogeneous nature of this cell population. Herein, we found that common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs) preferentially differentiate into PACs compared with megakaryocyte-erythrocyte progenitors, hematopoietic stem cells, and common lymphoid progenitors. In vivo hindlimb ischemia studies and Matrigel plug assays verified the enhanced neovascularization properties uniquely associated with PACs derived from CMPs and GMPs. Taken together, these observations identify CMPs and GMPs as key bone marrow progenitors for optimal PAC function in vitro and in vivo and provide a foundation for novel therapeutic approaches to modulate angiogenesis.
authors.affiliation: Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Akm Khyrul
authors.initials: AK
authors.lastname: Wara
authors.forename: Kevin
authors.initials: K
authors.lastname: Croce
authors.forename: ShiYin
authors.initials: S
authors.lastname: Foo
authors.forename: Xinghui
authors.initials: X
authors.lastname: Sun
authors.forename: Basak
authors.initials: B
authors.lastname: Icli
authors.forename: Yevgenia
authors.initials: Y
authors.lastname: Tesmenitsky
authors.forename: Fehim
authors.initials: F
authors.lastname: Esen
authors.forename: Anthony
authors.initials: A
authors.lastname: Rosenzweig
authors.forename: Mark W
authors.initials: MW
authors.lastname: Feinberg
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D055014:Granulocyte-Macrophage Progenitor Cells / Q000502:physiology*; D006614:Hindlimb; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D023461:Myeloid Progenitor Cells / Q000502:physiology*; D017202:Myocardial Ischemia / Q000503:physiopathology; D018919:Neovascularization, Physiologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers; D019408:Platelet Endothelial Cell Adhesion Molecule-1