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Optogenetic control of mesenchymal cell fate towards precise bone regeneration. | LitMetric

Optogenetic control of mesenchymal cell fate towards precise bone regeneration.

Theranostics

Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou 510055, China.

Published: August 2020

AI Article Synopsis

  • The study explores how to control cell fate for regenerative medicine using a technique called optogenetics, which manipulates gene expression with light.
  • Researchers combined the Lhx8 and BMP2 genes into a customized optogenetic system to regulate mesenchymal stem cell (MSC) activities: Lhx8 is always active, while BMP2 can be activated by blue light.
  • Animal experiments demonstrated that blue light effectively enhances bone regeneration when used in a scaffold containing genetically modified MSCs, highlighting the potential of this method for targeted therapies in regenerative medicine.

Article Abstract

Spatial-temporal control of cell fate 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. 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. 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 . By animal study, we found that blue light could fine-tune the regeneration . 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. 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857041PMC
http://dx.doi.org/10.7150/thno.36455DOI Listing

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