Review
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Apr 26, 2025; 17(4): 102945
Published online Apr 26, 2025. doi: 10.4252/wjsc.v17.i4.102945
Stem cell therapy for intervertebral disc degeneration: Clinical progress with exosomes and gene vectors
Zhi-Peng Li, Han Li, Yu-Hua Ruan, Peng Wang, Meng-Ting Zhu, Wei-Ping Fu, Rui-Bo Wang, Xiao-Dong Tang, Qi Zhang, Sen-Li Li, He Yin, Cheng-Jin Li, Yi-Gong Tian, Rui-Ning Han, Yao-Bin Wang, Chang-Jiang Zhang
Zhi-Peng Li, Yu-Hua Ruan, Peng Wang, Wei-Ping Fu, Rui-Bo Wang, Xiao-Dong Tang, Qi Zhang, Sen-Li Li, He Yin, Cheng-Jin Li, Yao-Bin Wang, Chang-Jiang Zhang, Second Department of Orthopedics, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Zhi-Peng Li, Tianjian Advanced Biomedical Laboratory, Zhengzhou University, Zhengzhou 450001, Henan Province, China
Han Li, Department of Orthopedics, Affiliated Dongyang Hospital of Wenzhou Medical University, Jinhua 322100, Zhejiang Province, China
Meng-Ting Zhu, Department of Neurology, Union Medical College Hospital of Fujian Medical University, Fuzhou 350001, Fujian Province, China
Yi-Gong Tian, Rui-Ning Han, Third Department of Orthopedics, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Yao-Bin Wang, Henan Key Laboratory for Helicobacter pylori and Digestive Tract Microecology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Co-first authors: Zhi-Peng Li and Han Li.
Co-corresponding authors: Yao-Bin Wang and Chang-Jiang Zhang.
Author contributions: Li ZP and Li H contributed equally to this work and are co-first authors of this manuscript; Li ZP and Li H conceptualized and designed the study, developed the research framework, and created the artwork; Ruan YH and Wang P were responsible for data curation and formal analysis, ensuring the accuracy and consistency of the results; Zhu MT developed the software essential for data processing; Fu WP supervised the project, providing critical oversight and guidance; Wang RB and Tang XD performed critical revisions of the manuscript, enhancing its clarity and scientific rigor; Zhang Q and Li SL conducted the validation and refined the methodology; Yin H and Li CJ managed resources and visualization, ensuring the effective presentation of findings, and contributed to the investigation and conducted key experimental work; Zhang CJ was responsible for funding acquisition and project administration, securing essential resources and ensuring efficient project coordination; Wang YB and Zhang CJ conducted the literature review, performed the data analysis and interpretation, and reviewed and edited the final manuscript; Wang YB and Zhang CJ contributed equally to this manuscript, and both served as co-corresponding authors because of their significant roles in resource management, data interpretation, and manuscript finalization; Each corresponding author made distinct and critical contributions to collaborative writing and the final review of the manuscript.
Supported by Henan Province Key Research and Development Program, No. 231111311000; Henan Provincial Science and Technology Research Project, No. 232102310411; Henan Province Medical Science and Technology Key Project, No. LHGJ20220566 and No. LHGJ20240365; Henan Province Medical Education Research Project, No. WJLX2023079; and Zhengzhou Medical and Health Technology Innovation Guidance Program, No. 2024YLZDJH022.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Chang-Jiang Zhang, MD, Chief Physician, Professor, Second Department of Orthopedics, The Fifth Affiliated Hospital of Zhengzhou University, No. 3 Kangfu Qianjie, Erqi District, Zhengzhou 450052, Henan Province, China. changjiangzhang1968@outlook.com
Received: November 5, 2024
Revised: January 25, 2025
Accepted: March 10, 2025
Published online: April 26, 2025
Processing time: 171 Days and 17.5 Hours
Abstract

Intervertebral disc degeneration is a leading cause of lower back pain and is characterized by pathological processes such as nucleus pulposus cell apoptosis, extracellular matrix imbalance, and annulus fibrosus rupture. These pathological changes result in disc height loss and functional decline, potentially leading to disc herniation. This comprehensive review aimed to address the current challenges in intervertebral disc degeneration treatment by evaluating the regenerative potential of stem cell-based therapies, with a particular focus on emerging technologies such as exosomes and gene vector systems. Through mechanisms such as differentiation, paracrine effects, and immunomodulation, stem cells facilitate extracellular matrix repair and reduce nucleus pulposus cell apoptosis. Despite recent advancements, clinical applications are hindered by challenges such as hypoxic disc environments and immune rejection. By analyzing recent preclinical and clinical findings, this review provided insights into optimizing stem cell therapy to overcome these obstacles and highlighted future directions in the field.

Keywords: Exosomes; Extracellular matrix repair; Gene vector system; Hypoxic environment; Intervertebral disc degeneration; Mesenchymal stem cells; Regenerative medicine; Stem cell therapy

Core Tip: The application of stem cell therapy in intervertebral disc degeneration has shown significant regenerative potential. Through differentiation, paracrine effects, and immunomodulation, stem cells can repair damaged extracellular matrix and slow the degenerative process. Emerging technologies such as exosomes and gene vector systems further enhance the therapeutic effects of stem cells, improving cell survival rates and regenerative capabilities. However, the long-term survival of stem cells in a hypoxic environment, the optimal injection dosage, and their long-term safety still requires further investigation. Future interdisciplinary collaboration will drive the clinical translation of stem cell therapy, making it a standard option for the treatment of intervertebral disc degeneration.