TY - JOUR
T1 - Delivery of coenzyme Q10 loaded micelle targets mitochondrial ROS and enhances efficiency of mesenchymal stem cell therapy in intervertebral disc degeneration
AU - Sun, Junyuan
AU - Yang, Fei
AU - Wang, Lianlei
AU - Yu, Haichao
AU - Yang, Zhijie
AU - Wei, Jingjing
AU - Vasilev, Krasimir
AU - Zhang, Xuesong
AU - Liu, Xinyu
AU - Zhao, Yunpeng
PY - 2023/5
Y1 - 2023/5
N2 - Stem cell transplantation has been proved a promising therapeutic instrument in intervertebral disc degeneration (IVDD). However, the elevation of oxidative stress in the degenerated region impairs the efficiency of mesenchymal stem cells (BMSCs) transplantation treatment via exaggeration of mitochondrial ROS and promotion of BMSCs apoptosis. Herein, we applied an emulsion-confined assembly method to encapsulate Coenzyme Q10 (Co-Q10), a promising hydrophobic antioxidant which targets mitochondria ROS, into the lecithin micelles, which renders the insoluble Co-Q10 dispersible in water as stable colloids. These micelles are injectable, which displayed efficient ability to facilitate Co-Q10 to get into BMSCs in vitro, and exhibited prolonged release of Co-Q10 in intervertebral disc tissue of animal models. Compared to mere use of Co-Q10, the Co-Q10 loaded micelle possessed better bioactivities, which elevated the viability, restored mitochondrial structure as well as function, and enhanced production of ECM components in rat BMSCs. Moreover, it is demonstrated that the injection of this micelle with BMSCs retained disc height and alleviated IVDD in a rat needle puncture model. Therefore, these Co-Q10 loaded micelles play a protective role in cell survival and differentiation through antagonizing mitochondrial ROS, and might be a potential therapeutic agent for IVDD.
AB - Stem cell transplantation has been proved a promising therapeutic instrument in intervertebral disc degeneration (IVDD). However, the elevation of oxidative stress in the degenerated region impairs the efficiency of mesenchymal stem cells (BMSCs) transplantation treatment via exaggeration of mitochondrial ROS and promotion of BMSCs apoptosis. Herein, we applied an emulsion-confined assembly method to encapsulate Coenzyme Q10 (Co-Q10), a promising hydrophobic antioxidant which targets mitochondria ROS, into the lecithin micelles, which renders the insoluble Co-Q10 dispersible in water as stable colloids. These micelles are injectable, which displayed efficient ability to facilitate Co-Q10 to get into BMSCs in vitro, and exhibited prolonged release of Co-Q10 in intervertebral disc tissue of animal models. Compared to mere use of Co-Q10, the Co-Q10 loaded micelle possessed better bioactivities, which elevated the viability, restored mitochondrial structure as well as function, and enhanced production of ECM components in rat BMSCs. Moreover, it is demonstrated that the injection of this micelle with BMSCs retained disc height and alleviated IVDD in a rat needle puncture model. Therefore, these Co-Q10 loaded micelles play a protective role in cell survival and differentiation through antagonizing mitochondrial ROS, and might be a potential therapeutic agent for IVDD.
KW - Coenzyme Q10
KW - Intervertebral disc degeneration
KW - Mesenchymal stem cell
KW - Micelle
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=85142296544&partnerID=8YFLogxK
U2 - 10.1016/j.bioactmat.2022.10.019
DO - 10.1016/j.bioactmat.2022.10.019
M3 - Article
AN - SCOPUS:85142296544
SN - 2452-199X
VL - 23
SP - 247
EP - 260
JO - Bioactive Materials
JF - Bioactive Materials
ER -