Repair of Critical-Sized Rat Calvarial Defects Using Genetically Engineered Bone Marrow-Derived Mesenchymal Stem Cells Overexpressing Hypoxia-Inducible Factor-1α

被引：104

作者：

Zou, Duohong ^{[2
,3
,7
]}

Zhang, Zhiyuan ^{[3
]}

Ye, Dongxia ^{[3
]}

Tang, Aifa ^{[5
]}

Deng, Lianfu ^{[4
]}

Han, Wei ^{[6
]}

Zhao, Jun ^{[3
]}

Wang, Shuhong ^{[2
]}

Zhang, Wenjie ^{[3
]}

Zhu, Chao ^{[3
]}

Zhou, Jian ^{[7
]}

He, Jiacai ^{[7
]}

Wang, Yuanyin ^{[7
]}

Xu, Feng ^{[3
]}

Huang, Yuanliang ^{[1
]}

Jiang, Xinquan ^{[3
]}

机构：

[1] Tongji Univ, Shanghai E Hosp, Dept Stomatol, Shanghai 200120, Peoples R China

[2] Tongji Univ, Sch Stomatol, Shanghai 200120, Peoples R China

[3] Shanghai Jiao Tong Univ, Peoples Hosp 9, Dept Oral & Maxillofacial Surg, Shanghai Key Lab Stomatol,Sch Med, Shanghai 200030, Peoples R China

[4] Shanghai Jiao Tong Univ, Shanghai Ruijin Hosp, Dept Orthopaed, Shanghai Inst Orthopaed & Traumatol,Sch Med, Shanghai 200030, Peoples R China

[5] Shenzhen Univ, Affiliated Hosp 1, Peoples Hosp Shenzhen 2, Shenzhen, Peoples R China

[6] Nanjing Stomatol Hosp, Dept Oral & Maxillofacial Surg, Nanjing, Peoples R China

[7] Anhui Med Univ, Stomatol Hosp, Sch Stomatol, Dept Oral & Maxillofacial Surg, Hefei, Peoples R China

来源：

STEM CELLS | 2011年 / 29卷 / 09期

基金：

中国国家自然科学基金;

关键词：

Hypoxia-inducible factor-1 alpha; Bone marrow-derived mesenchymal stem cells; Osteogenesis; Gene therapy; Bone regeneration; GENE-EXPRESSION; STROMAL CELLS; IN-VITRO; HIF-1-ALPHA; TISSUE; REGENERATION; ANGIOGENESIS; THERAPY; HYDROXYAPATITE; INDUCTION;

D O I：

10.1002/stem.693

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

The processes of angiogenesis and bone formation are coupled both temporally and spatially during bone repair. Bone marrow-derived mesenchymal stem cells (BMSCs) have been effectively used to heal critical-size bone defects. Enhancing their ability to undergo angiogenic and osteogenic differentiation will enhance their potential use in bone regeneration. Hypoxia-inducible factor-1 alpha (HIF-1 alpha) has recently been identified as a major regulator of angiogenic-osteogenic coupling. In this study, we tested the hypothesis that HIF-1 alpha gene therapy could be used to promote the repair of critical-sized bone defects. Using lentivirus-mediated delivery of wild-type (HIF) or constitutively active HIF-1 alpha (cHIF), we found that in cultured BMSCs in vitro, HIF and cHIF significantly enhanced osteogenic and angiogenic mRNA and protein expression when compared with the LacZ group. We found that HIF-1 alpha-overexpressing BMSCs dramatically improved the repair of critical-sized calvarial defects, including increased bone volume, bone mineral density, blood vessel number, and blood vessel area in vivo. These data confirm the essential role of HIF-1 alpha modified BMSCs in angiogenesis and osteogenesis in vitro and in vivo. STEM CELLS 2011;29:1380-1390

引用

页码：1380 / 1390

页数：11

共 34 条

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