Critical-size calvarial bone defects healing in a mouse model with silk scaffolds and SATB2-modified iPSCs

被引：136

作者：

Ye, Jin-Hai ^{[1
,2
,3
]}

Xu, Yuan-Jin ^{[1
,3
]}

Gao, Jun ^{[4
]}

Yan, Shi-Guo ^{[1
,5
]}

Zhao, Jun ^{[1
,3
]}

Tu, Qisheng ^{[1
]}

Zhang, Jin ^{[1
,5
]}

Duan, Xue-Jing ^{[1
,5
]}

Sommer, Cesar A. ^{[6
]}

Mostoslavsky, Gustavo ^{[6
]}

Kaplan, David L. ^{[7
]}

Wu, Yu-Nong ^{[2
]}

Zhang, Chen-Ping ^{[3
]}

Wang, Lin ^{[2
]}

Chen, Jake ^{[1
]}

机构：

[1] Tufts Univ, Sch Dent Med, Div Oral Biol, Boston, MA 02111 USA

[2] Nanjing Med Univ, Sch Stomatol, Inst Stomatol, Nanjing 210029, Jiangsu Prov, Peoples R China

[3] Shanghai Jiao Tong Univ, Peoples Hosp 9, Dept Oral & Maxillofacial Surg, Sch Med,Shanghai Key Lab Stomatol, Shanghai 200011, Peoples R China

[4] Nanjing Univ, Model Anim Res Ctr, MOE Key Lab Model Anim Dis Study, Nanjing 210061, Peoples R China

[5] Shandong Univ, Sch Stomatol, Jinan 250012, Peoples R China

[6] Boston Univ, Sch Med, Ctr Regenerat Med CReM, Sect Gastroenterol,Dept Med, Boston, MA 02118 USA

[7] Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA

来源：

BIOMATERIALS | 2011年 / 32卷 / 22期

基金：

中国国家自然科学基金;

关键词：

Induced pluripotent stem cells; Silk scaffold; SATB2; Osteogenesis; PLURIPOTENT STEM-CELLS; OSTEOBLAST DIFFERENTIATION; IN-VITRO; GENERATION; FIBROBLASTS; SATB2; GENE; INDUCTION; REPAIR; RATS;

D O I：

10.1016/j.biomaterials.2011.03.053

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Induced pluripotent stem cells (iPSCs) can differentiate into mineralizing cells and thus have a great potential in application in engineered bone substitutes with bioactive scaffolds in regeneration medicine. In the current study we characterized and demonstrated the pluripotency and osteogenic differentiation of mouse iPSCs. To enhance the osteogenic differentiation of iPSCs, we then transduced the iPSCs with the potent transcription factor, nuclear matrix protein SATB2. We observed that in SATB2-overexpressing iPSCs there were increased mineral nodule formation and elevated mRNA levels of key osteogenic genes, osterix (OSX), Runx2, bone sialoprotein (BSP) and osteocalcin (OCN). Moreover, the mRNA levels of HoxA2 was reduced after SATB2 overexpression in iPSCs. The SATB2-overexpressing iPSCs were then combined with silk scaffolds and transplanted into critical-size calvarial bone defects created in nude mice. Five weeks post-surgery, radiological and micro-CT analysis revealed enhanced new bone formation in calvarial defects in SATB2 group. Histological analysis also showed increased new bone formation and mineralization in the SATB2 group. In conclusion, the results demonstrate that SATB2 facilitates the differentiation of iPSCs towards osteoblast-lineage cells by repressing HoxA2 and augmenting the functions of the osteoblast determinants Runx2, BSP and OCN. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：5065 / 5076

页数：12

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