1. Academic Validation
  2. Engineering Extracellular Vesicles Restore the Impaired Cellular Uptake and Attenuate Intervertebral Disc Degeneration

Engineering Extracellular Vesicles Restore the Impaired Cellular Uptake and Attenuate Intervertebral Disc Degeneration

  • ACS Nano. 2021 Sep 28;15(9):14709-14724. doi: 10.1021/acsnano.1c04514.
Zhiwei Liao 1 Hui Liu 1 Liang Ma 1 Jie Lei 1 Bide Tong 1 Gaocai Li 1 Wencan Ke 1 Kun Wang 1 Xiaobo Feng 1 Wenbin Hua 1 Shuai Li 1 Cao Yang 1
Affiliations

Affiliation

  • 1 Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Abstract

Extracellular vesicles (EVs) are potential alternatives for mesenchymal stem cells (MSCs) in the treatment of musculoskeletal degenerative diseases, including intervertebral disc degeneration (IDD). Usually, EVs are internalized and then deliver bioactive molecules that impart phenotypic changes in recipient cells. For effective utilization of EVs in the IDD therapy, understanding the mechanism of EV uptake is of vital importance. In this study, we found that EVs delivered antioxidant proteins to protect against Pyroptosis of nucleus pulposus cells (NPCs). In particular, the therapeutic effect of EVs decreased in TNF-α-treated NPCs due to the impaired caveolae-mediated endocytosis pathway. Transcriptome Sequencing and functional verification revealed that caveolae associated protein 2 (Cavin-2) played an important role in the uptake process of EVs. We then constructed the Cavin-2-modified engineering EVs via the gene-editing of parental MSCs. These kinds of modified EVs presented an improved uptake rate in TNF-α-treated NPCs, which effectively ameliorated the cell death of NPCs in a three-dimensional hydrogel culture model and retarded the progression of IDD in the ex vivo organ culture model. Collectively, these findings illustrate the mechanism of EV uptake in NPCs and explore the application of engineering EVs in the treatment of IDD.

Keywords

endocytosis; extracellular vesicles; intervertebral disc degeneration; mesenchymal stem cells; organ culture.

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