Enhancement of neovascularization with mobilized blood cells transplantaion: supply of angioblasts and angiogenic cytokines.
We have recently provided evidence that transplantation of G-CSF mobilized peripheral blood mononuclear cells (M-PBMNCs) improves limb ischemia in diabetic patients. This method represents a simple, safe, effective, and novel therapeutic approach for diabetic ischemia. Here we investigated the mechanisms by which mobilized blood cells transplantation improves limb ischemia. Unilateral hindlimb ischemia was surgically induced in streptozotocin-induced diabetic nude mice, and they were intramuscularly injected 10(6) M-PBMNCs, or human umbilical vein endothelial cells (HUVECs), PBS controls. We compared their blood-flow restoration via laser Doppler perfusion image (LDPI), angiogenesis via histological determination of capillary density. Physiological and histological assessment revealed an acceleration of ischemia recovery and increase in capillary density with less apoptosis in M-PBMNCs group, compared with those in HUVECs and PBS groups. In vivo noninvasive imaging and immunofluorescence revealed the survival, migration, proliferation, differentiation, and incorporation of M-PBMNCs into foci of vessel networks. More angioblasts were from blood cells after mobilization, and they also produced a number of antiapoptotic and proagniogenic factors that promoted angiogenesis in vivo. M-PBMNCs and its conditioned medium augmented the vessel formation in matrigel plugs in vivo. Thus, transplantation of M-PBMNCs achieved therapeutic neovascularization via supply of abundant angioblasts and angiogenic factors.
Zhou
Bin
B
State Key Laboratory of Experimental Hematology, National Research Center for Stem Cell Engineering and Technology, Institute of Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Liu
Peng Xia
PX
Lan
Hai Feng
HF
Fang
Zhi Hong
ZH
Han
Zhi Bo
ZB
Ren
He
H
Poon
Man-Chiu
MC
Han
Zhong Chao
ZC
D042501:Angiogenic Proteins / Q000096:biosynthesis*; D000818:Animals; D002196:Capillaries / Q000254:growth & development; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003925:Diabetic Angiopathies / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004730:Endothelium, Vascular / Q000166:cytology; D019650:Hematopoietic Stem Cell Mobilization; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007267:Injections; D007511:Ischemia / Q000150:complications / Q000473:pathology / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000502:physiology / Q000637:transplantation; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods; D012039:Regional Blood Flow
D042501:Angiogenic Proteins; D017077:Culture Media, Conditioned; D016207:Cytokines