Blood vessel formation in the tissue-engineered bone with the constitutively active form of HIF-1α mediated BMSCs

被引：115

作者：

Zou, Duohong ^{[1
,2
,3
]}

Zhang, Zhiyuan ^{[1
]}

He, Jiacai ^{[3
]}

Zhang, Kai ^{[4
]}

Ye, Donxia ^{[1
]}

Han, Wei ^{[5
]}

Zhou, Jian ^{[3
]}

Wang, Yuanyin ^{[3
]}

Li, Quanli ^{[3
]}

Liu, Xin ^{[3
]}

Zhang, Xin ^{[2
]}

Wang, Shaoyi ^{[1
]}

Hu, Jingzhou ^{[1
]}

Zhu, Chao ^{[1
]}

Zhang, Wenjie ^{[1
]}

Zhou, Yong ^{[1
]}

Fu, Honghai ^{[1
]}

Huang, Yuanliang ^{[6
]}

Jiang, Xinquan ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Oral Bioengn Lab, Regenerat Med Lab,Sch Med,Shanghai Key Lab Stomat, Dept Prosthodont,Shanghai Res Inst Stomatol,Peopl, Shanghai 200011, Peoples R China

[2] Tongji Univ, Dept Oral & Maxillofacial Surg, Sch Stomatol, Shanghai 200072, Peoples R China

[3] Anhui Med Univ, Dept Oral & Maxillofacial Surg, Sch Stomatol, Stomatol Hosp, Hefei 230032, Peoples R China

[4] Bengbu Med Coll, Dept Stomatol, Affiliated Hosp 1, Bengbu, Anhui, Peoples R China

[5] Nanjing Stomatol Hosp, Dept Oral & Maxillofacial Surg, Nanjing 210008, Peoples R China

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

来源：

BIOMATERIALS | 2012年 / 33卷 / 07期

基金：

中国国家自然科学基金;

关键词：

HIF-1a; Angiogenesis; The tissue-engineered bone; Gene therapy; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; MESENCHYMAL STEM-CELLS; GENE-EXPRESSION; LIMB ISCHEMIA; FACTOR-I; CALVARIAL DEFECTS; ANGIOGENESIS; VEGF; GROWTH; VASCULARIZATION;

D O I：

10.1016/j.biomaterials.2011.11.053

中图分类号：

R318 [生物医学工程];

学科分类号：

100103 [病原生物学];

摘要：

The successful clinical outcome of the implanted tissue-engineered bone is dependent on the establishment of a functional vascular network. A gene-enhanced tissue engineering represents a promising approach for vascularization. Our previous study indicated that hypoxia-inducible factor-1 alpha (HIF-1 alpha) can up-regulate the expression of vascular endothelial growth factor (VEGF) and stromal-derived factor 1 (SDF-1) in bone mesenchymal stem cells (BMSCs). The angiogenesis is a co-ordinated process that requires the participation of multiple angiogenic factors. To further explore the angiogenic effect of HIF-1 alpha mediated stem cells, in this study, we systematically evaluated the function of HIF-1 alpha in enhancing BMSCs angiogenesis in vitro and in vivo. A constitutively active form of HIF-1 alpha (CA5) was inserted into a lentivirus vector and transduced into BMSCs, and its effect on vascularization and vascular remodeling was further evaluated in a rat critical-sized calvarial defects model with a gelatin sponge (GS) scaffold. The expression of the key angiogenic factors including VEGF, SDF-1, basic fibroblast growth factor (bFGF), placental growth factor (PLGF), angiopoietin 1 (ANGPT1), and stem cell factor (SCF) at both mRNAs and proteins levels in BMSCs were significantly enhanced by HIF-1 alpha overexpression compared to the in vitro control group. In addition, HIF-1 alpha-over expressing BMSCs showed dramatically improved blood vessel formation in the tissue-engineered bone as analyzed by photography of specimen, micro-CT, and histology. These data confirm the important role of HIF-1 alpha in angiogenesis in tissue-engineered bone. Improved understanding of the mechanisms of angiogenesis may offer exciting therapeutic opportunities for vascularization, vascular remodeling, and bone defect repair using tissue engineering strategies in the future. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：2097 / 2108

页数：12

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