Abstract

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.

Details

Title
BMP-2 and VEGF-A modRNAs in collagen scaffold synergistically drive bone repair through osteogenic and angiogenic pathways
Author
Geng Yingnan 1 ; Duan Huichuan 1 ; Xu, Liang 1 ; Witman Nevin 2 ; Yan Bingqian 3 ; Yu Zheyuan 1 ; Wang, Huijing 3 ; Tan, Yao 3 ; Lin, Liqin 1 ; Li, Dong 1 ; Bai Shanshan 1 ; Fritsche-Danielson, Regina 4 ; Yuan Jie 1   VIAFID ORCID Logo  ; Chien, Kenneth 2   VIAFID ORCID Logo  ; Wei, Min 1   VIAFID ORCID Logo  ; Fu, Wei 5   VIAFID ORCID Logo 

1  Shanghai Jiao Tong University, Department of Plastic and Reconstructive Surgery, Shanghai 9th People’s Hospital, School of Medicine, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293) 
2  Karolinska Institutet, Department of Medicine, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); Karolinska Institutet, Department of Cell and Molecular Biology, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626) 
3  Shanghai Jiao Tong University, Institute of Pediatric Translational Medicine, Shanghai Children’s Medical Center, School of Medicine, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293); Shanghai Jiao Tong University, Department of Pediatric Cardiothoracic Surgery, Shanghai Children’s Medical Center, School of Medicine, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293) 
4  AstraZeneca, Research and Early Clinical Development, Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, Gothenburg, Sweden (GRID:grid.418151.8) (ISNI:0000 0001 1519 6403) 
5  Shanghai Jiao Tong University, Institute of Pediatric Translational Medicine, Shanghai Children’s Medical Center, School of Medicine, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293); Shanghai Jiao Tong University, Department of Pediatric Cardiothoracic Surgery, Shanghai Children’s Medical Center, School of Medicine, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293); Shanghai Jiao Tong University, Shanghai Key Laboratory of Tissue Engineering, Shanghai 9th People’s Hospital, School of Medicine, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
23993642
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s42003-020-01606-9
ProQuest document ID
2478869066
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.