Erythroid cells play essential roles in angiogenesis by bone marrow cell implantation.
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.
Ozawa
Takuya
T
Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, Japan. takuya-o@med.niigata-u.ac.jp
Toba
Ken
K
Kato
Kiminori
K
Minagawa
Shiro
S
Saigawa
Takashi
T
Hanawa
Haruo
H
Makiyama
Yashiro
Y
Moriyama
Masato
M
Honma
Kei-Ichiro
K
Isoda
Manabu
M
Hasegawa
Go
G
Naito
Makoto
M
Takahashi
Masuhiro
M
Aizawa
Yoshifusa
Y
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
D018950:Lipopolysaccharide Receptors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D004921:Erythropoietin