title: Erythroid cells play essential roles in angiogenesis by bone marrow cell implantation.
abstract: Bone marrow cell implantation (BMI) has been utilized to treat patients with limb and heart ischemia. BMI provides angiogenic precursors and angiogenic cytokine-producing cells, especially erythroid cells. In this study, we induced in vitro angiogenesis cultures and in vivo BMI simulation using a murine limb ischemia model to examine the role of erythroid cells and the effect of erythropoietin (EPO). Human erythroid colonies (BFU-e) induced capillary networks around the colonies in vitro. Erythroid cells in human bone marrow produced vascular endothelial growth factor and placental growth factor. The angiogenic effects of erythroid cells were further amplified in the presence of EPO. Limb-ischemic mice were treated with BMI +/- EPO, and limb survival, blood flow recovery, and muscle histology were analyzed. Treatment with whole bone marrow cells + EPO significantly improved limb survival and blood flow. The cumulative effects of EPO on BMI induced and increase in capillary number and artery enlargement. Erythroid cells were essential for the in vivo effects of BMI, and CD14-positive cells supported the biological effects. In addition to the direct effect of EPO on angiogenesis, EPO showed indirect effect on angiogenesis through amplifying the angiogenic effects by erythroid cells supported by CD14-positive cells.
authors.affiliation: Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, Japan. takuya-o@med.niigata-u.ac.jp
authors.forename: Takuya
authors.initials: T
authors.lastname: Ozawa
authors.forename: Ken
authors.initials: K
authors.lastname: Toba
authors.forename: Kiminori
authors.initials: K
authors.lastname: Kato
authors.forename: Shiro
authors.initials: S
authors.lastname: Minagawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Saigawa
authors.forename: Haruo
authors.initials: H
authors.lastname: Hanawa
authors.forename: Yashiro
authors.initials: Y
authors.lastname: Makiyama
authors.forename: Masato
authors.initials: M
authors.lastname: Moriyama
authors.forename: Kei-Ichiro
authors.initials: K
authors.lastname: Honma
authors.forename: Manabu
authors.initials: M
authors.lastname: Isoda
authors.forename: Go
authors.initials: G
authors.lastname: Hasegawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Naito
authors.forename: Masuhiro
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology; D041905:Erythroid Cells / Q000166:cytology*; D015672:Erythroid Precursor Cells / Q000378:metabolism; D004921:Erythropoietin / Q000378:metabolism; D005260:Female; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017202:Myocardial Ischemia / Q000628:therapy; D018919:Neovascularization, Physiologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D018950:Lipopolysaccharide Receptors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D004921:Erythropoietin