BMP-2 and VEGF-A modRNAs in collagen scaffold synergistically drive bone repair through osteogenic and angiogenic pathways

被引：78

作者：

Geng, Yingnan ^{[1
]}

Duan, Huichuan ^{[1
]}

Xu, Liang ^{[1
]}

Witman, Nevin ^{[2
,3
]}

Yan, Bingqian ^{[4
,5
]}

Yu, Zheyuan ^{[1
]}

Wang, Huijing ^{[4
,5
]}

Tan, Yao ^{[4
,5
]}

Lin, Liqin ^{[1
]}

Li, Dong ^{[1
]}

Bai, Shanshan ^{[1
]}

Fritsche-Danielson, Regina ^{[6
]}

Yuan, Jie ^{[1
]}

Chien, Kenneth ^{[2
,3
]}

Wei, Min ^{[1
]}

Fu, Wei ^{[4
,5
,7
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Plast & Reconstruct Surg, 639 Zhi Zao Ju Rd, Shanghai 200011, Peoples R China

[2] Karolinska Inst, Dept Med, Stockholm, Sweden

[3] Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden

[4] Shanghai Jiao Tong Univ, Inst Pediat Translat Med, Sch Med, Shanghai Childrens Med Ctr, 1678 Dong Fang Rd, Shanghai 200127, Peoples R China

[5] Shanghai Jiao Tong Univ, Sch Med, Dept Pediat Cardiothorac Surg, Shanghai Childrens Med Ctr, 1678 Dong Fang Rd, Shanghai 200127, Peoples R China

[6] AstraZeneca, Biopharmaceut R&D, Cardiovasc Renal & Metab, Res & Early Clin Dev, Pepparedsleden 1, S-43183 Gothenburg, Sweden

[7] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Shanghai Key Lab Tissue Engn, Shanghai 200011, Peoples R China

来源：

COMMUNICATIONS BIOLOGY | 2021年 / 4卷 / 01期

基金：

中国国家自然科学基金;

关键词：

D O I：

10.1038/s42003-020-01606-9

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Bone has a remarkable potential for self-healing and repair, yet several injury types are non-healing even after surgical or non-surgical treatment. Regenerative therapies that induce bone repair or improve the rate of recovery are being intensely investigated. Here, we probed the potential of bone marrow stem cells (BMSCs) engineered with chemically modified mRNAs (modRNA) encoding the hBMP-2 and VEGF-A gene to therapeutically heal bone. Induction of osteogenesis from modRNA-treated BMSCs was confirmed by expression profiles of osteogenic related markers and the presence of mineralization deposits. To test for therapeutic efficacy, a collagen scaffold inoculated with modRNA-treated BMSCs was explored in an in vivo skull defect model. We show that hBMP-2 and VEGF-A modRNAs synergistically drive osteogenic and angiogenic programs resulting in superior healing properties. This study exploits chemically modified mRNAs, together with biomaterials, as a potential approach for the clinical treatment of bone injury and defects. Geng et al. evaluate bone marrow stem cell (BMSC)-based system to deliver modified RNAs of BMP-2 and VEGF to enhance bone regeneration. They test its therapeutic efficacy in vivo on a rat skull defect model by inoculating these BMSCs in a collagen scaffold. This construct synergistically drives osteogenic and angiogenic pathways and can be a new approach for clinical treatment of bone injuries and defects.

引用

页数：14

共 60 条

[51] Bilayered BMP2 Eluting Coatings on Graphene Foam by Electrophoretic Deposition: Electroresponsive BMP2 Release and Enhancement of Osteogenic Differentiation [J].