Exploring extracellular vesicles as novel therapeutic agents for intervertebral disc degeneration: delivery, applications, and mechanisms

Abstract Intervertebral disc degeneration is a multifactorial degenerative disease that poses a significant threat to the health of the elderly population. Current treatments primarily focus on physical therapy, medication, and surgery to alleviate symptoms associated with disc compression but do no...

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Main Authors: Yuxin Jin, Ouqiang Wu, Zhihua Chen, Linjie Chen, Kai Zhang, Qizhu Chen, Haijun Tian, Xinzhou Wang, Morgan Jones, Kenny Yat Hong Kwan, Yan Michael Li, Pooyan Makvandi, Xiangyang Wang, Xiang Hai, Jun Zhang, Aimin Wu
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Stem Cell Research & Therapy
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Online Access:https://doi.org/10.1186/s13287-025-04299-1
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author Yuxin Jin
Ouqiang Wu
Zhihua Chen
Linjie Chen
Kai Zhang
Qizhu Chen
Haijun Tian
Xinzhou Wang
Morgan Jones
Kenny Yat Hong Kwan
Yan Michael Li
Pooyan Makvandi
Xiangyang Wang
Xiang Hai
Jun Zhang
Aimin Wu
author_facet Yuxin Jin
Ouqiang Wu
Zhihua Chen
Linjie Chen
Kai Zhang
Qizhu Chen
Haijun Tian
Xinzhou Wang
Morgan Jones
Kenny Yat Hong Kwan
Yan Michael Li
Pooyan Makvandi
Xiangyang Wang
Xiang Hai
Jun Zhang
Aimin Wu
author_sort Yuxin Jin
collection DOAJ
description Abstract Intervertebral disc degeneration is a multifactorial degenerative disease that poses a significant threat to the health of the elderly population. Current treatments primarily focus on physical therapy, medication, and surgery to alleviate symptoms associated with disc compression but do not address the progression of degeneration. Therefore, this review aimed to explore the potential of extracellular vesicle therapy as a novel preventive strategy to delay degeneration and enhance tissue repair in intervertebral discs. We cover the pathogenic mechanisms underlying intervertebral disc degeneration, including inflammation, apoptosis, pyroptosis, ferroptosis, autophagy dysregulation, and the roles of non-coding RNAs. Subsequently, we discussed the therapeutic potential of extracellular vesicles and their molecular components, such as proteins, RNAs, and lipids, in modulating these pathways to counter intervertebral disc degeneration. We provides a comprehensive review of the significant role of extracellular vesicle cargo in mediating repair mechanisms. It discusses the functional enhancement advantages exhibited by extracellular vesicles under current bioengineering modifications and drug loading. The challenges and future prospects of utilizing extracellular vesicle therapy to treat this degenerative condition are also summarized. Graphical abstract
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publishDate 2025-05-01
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series Stem Cell Research & Therapy
spelling doaj-art-c9a2f9d9d41d4c1f8d13baee21c9f8892025-08-20T02:11:09ZengBMCStem Cell Research & Therapy1757-65122025-05-0116112910.1186/s13287-025-04299-1Exploring extracellular vesicles as novel therapeutic agents for intervertebral disc degeneration: delivery, applications, and mechanismsYuxin Jin0Ouqiang Wu1Zhihua Chen2Linjie Chen3Kai Zhang4Qizhu Chen5Haijun Tian6Xinzhou Wang7Morgan Jones8Kenny Yat Hong Kwan9Yan Michael Li10Pooyan Makvandi11Xiangyang Wang12Xiang Hai13Jun Zhang14Aimin Wu15Department of Orthopaedics, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Orthopaedics, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Orthopaedics, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Orthopaedics, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityShanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Clinic of Spine Center, Xinhua Hospital, Shanghai Jiaotong University School of MedicineDepartment of Orthopaedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Orthopaedics, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversitySpine Unit, The Royal Orthopaedic HospitalDepartment of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Neurosurgery, University of Rochester Medical CenterUniversity Centre for Research & Development, Chandigarh UniversityDepartment of Orthopaedics, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityEcological-Environment & Health College (EEHC), Zhejiang A & F UniversityDepartment of Orthopedics, Zhejiang Provincial People’s Hospital Bijie HospitalDepartment of Orthopaedics, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityAbstract Intervertebral disc degeneration is a multifactorial degenerative disease that poses a significant threat to the health of the elderly population. Current treatments primarily focus on physical therapy, medication, and surgery to alleviate symptoms associated with disc compression but do not address the progression of degeneration. Therefore, this review aimed to explore the potential of extracellular vesicle therapy as a novel preventive strategy to delay degeneration and enhance tissue repair in intervertebral discs. We cover the pathogenic mechanisms underlying intervertebral disc degeneration, including inflammation, apoptosis, pyroptosis, ferroptosis, autophagy dysregulation, and the roles of non-coding RNAs. Subsequently, we discussed the therapeutic potential of extracellular vesicles and their molecular components, such as proteins, RNAs, and lipids, in modulating these pathways to counter intervertebral disc degeneration. We provides a comprehensive review of the significant role of extracellular vesicle cargo in mediating repair mechanisms. It discusses the functional enhancement advantages exhibited by extracellular vesicles under current bioengineering modifications and drug loading. The challenges and future prospects of utilizing extracellular vesicle therapy to treat this degenerative condition are also summarized. Graphical abstracthttps://doi.org/10.1186/s13287-025-04299-1Intervertebral disc degenerationLower back painExtracellular vesiclesExosomes
spellingShingle Yuxin Jin
Ouqiang Wu
Zhihua Chen
Linjie Chen
Kai Zhang
Qizhu Chen
Haijun Tian
Xinzhou Wang
Morgan Jones
Kenny Yat Hong Kwan
Yan Michael Li
Pooyan Makvandi
Xiangyang Wang
Xiang Hai
Jun Zhang
Aimin Wu
Exploring extracellular vesicles as novel therapeutic agents for intervertebral disc degeneration: delivery, applications, and mechanisms
Stem Cell Research & Therapy
Intervertebral disc degeneration
Lower back pain
Extracellular vesicles
Exosomes
title Exploring extracellular vesicles as novel therapeutic agents for intervertebral disc degeneration: delivery, applications, and mechanisms
title_full Exploring extracellular vesicles as novel therapeutic agents for intervertebral disc degeneration: delivery, applications, and mechanisms
title_fullStr Exploring extracellular vesicles as novel therapeutic agents for intervertebral disc degeneration: delivery, applications, and mechanisms
title_full_unstemmed Exploring extracellular vesicles as novel therapeutic agents for intervertebral disc degeneration: delivery, applications, and mechanisms
title_short Exploring extracellular vesicles as novel therapeutic agents for intervertebral disc degeneration: delivery, applications, and mechanisms
title_sort exploring extracellular vesicles as novel therapeutic agents for intervertebral disc degeneration delivery applications and mechanisms
topic Intervertebral disc degeneration
Lower back pain
Extracellular vesicles
Exosomes
url https://doi.org/10.1186/s13287-025-04299-1
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