Shi ZJ, Ying XM, Liu W. Targeting mitochondrial quality control in osteoarthritis with GrpE-like 1-loaded synovial mesenchymal stromal/stem cell small extracellular vesicles. World J Stem Cells 2026; 18(2): 114303 [DOI: 10.4252/wjsc.v18.i2.114303]
Corresponding Author of This Article
Wei Liu, Department of Oral Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou 310009, Zhejiang Province, China. liuwei1982@zju.edu.cn
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Cell & Tissue Engineering
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Editorial
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Feb 26, 2026 (publication date) through Feb 17, 2026
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World Journal of Stem Cells
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1948-0210
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Shi ZJ, Ying XM, Liu W. Targeting mitochondrial quality control in osteoarthritis with GrpE-like 1-loaded synovial mesenchymal stromal/stem cell small extracellular vesicles. World J Stem Cells 2026; 18(2): 114303 [DOI: 10.4252/wjsc.v18.i2.114303]
World J Stem Cells. Feb 26, 2026; 18(2): 114303 Published online Feb 26, 2026. doi: 10.4252/wjsc.v18.i2.114303
Targeting mitochondrial quality control in osteoarthritis with GrpE-like 1-loaded synovial mesenchymal stromal/stem cell small extracellular vesicles
Zhuo-Jin Shi, Xiao-Mei Ying, Wei Liu
Zhuo-Jin Shi, School/Hospital of Stomatology, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
Xiao-Mei Ying, Wei Liu, Department of Oral Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
Author contributions: Shi ZJ and Ying XM conducted literature review and drafted the manuscript; Liu W conceptualized the study, provided critical revisions, and supervised the overall work.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Wei Liu, Department of Oral Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou 310009, Zhejiang Province, China. liuwei1982@zju.edu.cn
Received: September 16, 2025 Revised: November 2, 2025 Accepted: January 20, 2026 Published online: February 26, 2026 Processing time: 151 Days and 17.3 Hours
Abstract
Recent studies have demonstrated that synovial mesenchymal stem cell-derived small extracellular vesicles (EVs) engineered to deliver GrpE-like 1 activated PTEN-induced kinase 1-dependent mitophagy and restored chondrocyte homeostasis. This study revealed that interleukin-1β-challenged chondrocytes exhibited efficient cargo transfer, increased mitophagy signaling with reduced p62 levels, lower oxidative stress, and a shift toward matrix preservation, characterized by higher collagen II and aggrecan levels, and lower matrix metallopeptidase 13 and ADAM metallopeptidase with thrombospondin type 1 motif 5 levels. In a rat knee osteoarthritis model, intra-articular dosing preserved cartilage architecture and improved histological scores. Collectively, these findings suggest that EV-based delivery of mitochondrial regulators is a plausible disease-modifying strategy, rather than purely symptomatic care. Building on this evidence, this editorial distills key advances and outlines near-term research and translational priorities, including standardized EV characterization, pharmacokinetics, dosing, safety, and manufacturability. The suitability of GrpE-like 1-loaded small EVs for early-stage osteoarthritis was also evaluated.
Core Tip: This editorial frames GrpE-like 1-loaded synovial extracellular vesicles as a mitochondria-centric strategy for osteoarthritis and translates bench evidence into an executable roadmap. We operationalize identity/purity panels, dual-metric dose (particles and protein), shared exposure anchors, and a mechanism-linked potency assay for lot release and comparability. Early trials should prespecify Outcome Measures in Rheumatology-Osteoarthritis Research Society International endpoints with quantitative magnetic resonance imaging cartilage thickness as an exploratory structural anchor. Transparent method registration and time-bounded regulatory messaging are emphasized to improve reproducibility, cross-study comparison, and readiness for first-in-human evaluation.
