2. Academic Validation
  3. A Redox Homeostasis Modulatory Hydrogel with GLRX3+ Extracellular Vesicles Attenuates Disc Degeneration by Suppressing Nucleus Pulposus Cell Senescence

A Redox Homeostasis Modulatory Hydrogel with GLRX3+ Extracellular Vesicles Attenuates Disc Degeneration by Suppressing Nucleus Pulposus Cell Senescence

  • ACS Nano. 2023 Jul 11. doi: 10.1021/acsnano.3c01713.
Can Liu 1,  Lei Fan 2,  Ming Guan 1,  Qiangqiang Zheng 3,  Jiale Jin 1,  Xinchang Kang 4,  Zhongyang Gao 1,  Xiaoqian Deng 5,  Yifan Shen 1,  Guangyu Chu 1,  Jingyao Chen 6,  Zhiqiang Yu 7,  Lei Zhou 8,  Yue Wang 1
Affiliations

Affiliations

  • 1 Department of Orthopedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
  • 2 Department of Orthopedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • 3 Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou 310030, China.
  • 4 School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, China.
  • 5 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, China.
  • 6 Core Facilities, Zhejiang University School of Medicine, Hangzhou 310030, China.
  • 7 Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
  • 8 Guangzhou Key Laboratory of Spine Disease Prevention and Treatment, Department of Spine Surgery, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China.
PMID: 37432866 DOI: 10.1021/acsnano.3c01713
Abstract

Characterized by nucleus pulposus (NP) cell senescence and extracellular matrix (ECM) degradation, disc degeneration is a common pathology for various degenerative spinal disorders. To date, effective treatments for disc degeneration are absent. Here, we found that Glutaredoxin3 (GLRX3) is an important redox-regulating molecule associated with NP cell senescence and disc degeneration. Using a hypoxic preconditioning method, we developed GLRX3+ mesenchymal stem cell-derived extracellular vehicles (EVs-GLRX3), which enhanced the cellular antioxidant defense, thus preventing Reactive Oxygen Species (ROS) accumulation and senescence cascade expansion in vitro. Further, a disc tissue-like biopolymer-based supramolecular hydrogel, which was injectable, degradable, and ROS-responsive, was proposed to deliver EVs-GLRX3 for treating disc degeneration. Using a rat model of disc degeneration, we demonstrated that the EVs-GLRX3-loaded hydrogel attenuated mitochondrial damage, alleviated the NP senescence state, and restored ECM deposition by modulating the redox homeostasis. Our findings suggested that modulation of redox homeostasis in the disc can rejuvenate NP cell senescence and thus attenuate disc degeneration.

Keywords

GLRX3+ extracellular vesicles; antisenescence; disc degeneration; extracellular matrix hydrogel; redox homeostasis.

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