The role of fucosylation in the promotion of endothelial progenitor cells in neovascularization and bone repair.
Bone marrow-derived endothelial progenitor cells (EPCs) are being tested as a therapy to treat a variety of ischemic diseases. Poor homing to targeted tissues is one of the major factors limiting the therapeutic efficacy of EPCs. Here, we show that human cord blood-derived EPCs expressed little sialyl Lewis X (sLe(x)) antigen that is necessary for selectin-mediated cell-cell interactions. Expression of α1,3-fucosyltransferase VI (FucT VI) in the EPCs enhanced sLe(x) synthesis, E- and P-selectin-binding, and EPC adhesion to tumor necrosis factor-α-stimulated human umbilical vein endothelial cells in culture. In a mouse model of hind limb ischemia, in which EPCs were injected intravenously, FucT VI expression increased EPC homing, neovascularization, and blood flow in ischemic muscles. In another mouse model of femoral fracture, FucT VI-expressing EPCs were more efficient than control EPCs in targeting to peri-fracture tissues to enhance angiogenesis, blood flow and bone repair. These results indicate that fucosylated EPCs may be used to as an improved cellular source to treat ischemic diseases.
The Cyrus Tang Hematology Center, Soochow University, Suzhou 215123, China; The Second Affiliated Hospital, Soochow University, Suzhou 215004, China.
Shengxuan
S
Sun
The Cyrus Tang Hematology Center, Soochow University, Suzhou 215123, China.
Zhenzhen
Z
Liu
The Second Affiliated Hospital, Soochow University, Suzhou 215004, China.
Haibin
H
Zhou
The Second Affiliated Hospital, Soochow University, Suzhou 215004, China.
Guoqiang
G
Li
The Cyrus Tang Hematology Center, Soochow University, Suzhou 215123, China.
Meng
M
Liu
Department of Oncology, Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
Jiannan
J
Yao
The Cyrus Tang Hematology Center, Soochow University, Suzhou 215123, China.
Tiantian
T
Zhou
Department of Oncology, Chao-Yang Hospital, Capital Medical University, Beijing 100020, China. Electronic address: anguangyu@hotmail.com.
Guangyu
G
An
The Cyrus Tang Hematology Center, Soochow University, Suzhou 215123, China; Molecular Cardiology, Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: wuq@ccf.org.
Qingyu
Q
Wu
The Cyrus Tang Hematology Center, Soochow University, Suzhou 215123, China; The MOH Key Laboratory of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China. Electronic address: ningzhengdong@suda.edu.cn.
Ningzheng
N
Dong
D000818:Animals; D001846:Bone Development; D002448:Cell Adhesion; D042783:Endothelial Cells / Q000166:cytology; D005643:Fucose / Q000378:metabolism*; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007511:Ischemia / Q000628:therapy; D051379:Mice; D018919:Neovascularization, Physiologic; D013234:Stem Cells / Q000166:cytology*
D005643:Fucose
Angiogenesis; Bone repair; Endothelial progenitor cells; Fucosylation; Ischemic disease; Selectins