Optogenetic control of mesenchymal cell fate towards precise bone regeneration
| Autor: | Chenyu Guan, Baicheng Bao, Delan Huang, Zhicai Feng, Weicai Wang, Junqi Ling, Bin Cai, Chen Zhou, Jianhan Ren, Runze Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Bone Regeneration Medicine (miscellaneous) Bone Morphogenetic Protein 2 Bone Marrow Cells 02 engineering and technology Optogenetics Cell fate determination Biology Regenerative Medicine Regenerative medicine Bone morphogenetic protein 2 03 medical and health sciences gene expression control Osteogenesis Transforming Growth Factor beta proliferation and differentiation Animals Humans Mesenchymal stem cell proliferation Bone regeneration Pharmacology Toxicology and Pharmaceutics (miscellaneous) Tissue Scaffolds Regeneration (biology) Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells 021001 nanoscience & nanotechnology bone tissue regeneration Recombinant Proteins Cell biology Rats 030104 developmental biology HEK293 Cells Gene Expression Regulation 0210 nano-technology Research Paper |
| Zdroj: | Theranostics |
| ISSN: | 1838-7640 |
| Popis: | Rationale: Spatial-temporal control of cell fate in vivo is of great importance for regenerative medicine. Currently, there remain no practical strategies to tune cell-fate spatial-temporally. Optogenetics is a biological technique that widely used to control cell activity in genetically defined neurons in a spatiotemporal-specific manner by light. In this study, optogenetics was repurposed for precise bone tissue regeneration. Methods: Lhx8 and BMP2 genes, which are considered as the master genes for mesenchymal stem cell proliferation and differentiation respectively, were recombined into a customized optogenetic control system. In the system, Lhx8 was constitutively expressed, while BMP2 together with shLhx8 expression was driven by blue light. Results: As expected, blue light induced BMP2 expression and inactivated Lhx8 expression in cells infected with the optogenetic control system. Optogenetic control of BMP2 and Lhx8 expression inversely regulates MSC fate in vitro. By animal study, we found that blue light could fine-tune the regeneration in vivo. Blue light illumination significantly promotes bone regeneration when the scaffold was loaded with MSCs infected with adeno-Lhx8, GI-Gal4DBD, LOV-VP16, and BMP2-shLhx8. Conclusions: Together, our study revealed that optogenetic control of the master genes for mesenchymal stem cell proliferation and differentiation would be such a candidate strategy for precise regenerative medicine. |
| Databáze: | OpenAIRE |
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