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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Nov 26, 2025; 17(11): 114306
Published online Nov 26, 2025. doi: 10.4252/wjsc.v17.i11.114306
Published online Nov 26, 2025. doi: 10.4252/wjsc.v17.i11.114306
Exosomal delivery of GrpE-like 1 from synovial mesenchymal stem cells activates PINK1-mediated mitophagy for cartilage repair in osteoarthritis
Soumya Deep Phadikar, Department of Chemistry and Chemical Biology, Indian Institute of Technology (ISM), Dhanbad 826004, India
Ramya Lakshmi Rajendran, Byeong-Cheol Ahn, BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
Ramya Lakshmi Rajendran, Prakash Gangadaran, Byeong-Cheol Ahn, Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
Ramya Lakshmi Rajendran, Prakash Gangadaran, Byeong-Cheol Ahn, Cardiovascular Research Institute, Kyungpook National University, Daegu 41944, South Korea
Sathish Muthu, Central Research Laboratory, Meenakshi Medical College Hospital and Research Institute, Meenakshi Academy of Higher Education and Research, Kanchipuram 631552, Tamil Nadu, India
Sathish Muthu, Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
Byeong-Cheol Ahn, Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu 41944, South Korea
Co-first authors: Soumya Deep Phadikar and Ramya Lakshmi Rajendran.
Co-corresponding authors: Prakash Gangadaran and Byeong-Cheol Ahn.
Author contributions: Phadikar SD, Rajendran RL, Muthu S, Gangadaran P, and Ahn BC designed the overall concept and outline of the manuscript, contributed to the discussion and design of the manuscript, and contributed to the writing and editing of the manuscript, and review of the literature. Phadikar SD and Rajendran RL contributed equally to this study as co-first authors. Gangadaran P and Ahn BC contributed equally as corresponding authors.
Supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, No. NRF-2022R1I1A1A01068652.
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: Byeong-Cheol Ahn, MD, PhD, Department of Nuclear Medicine, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, South Korea. abc2000@knu.ac.kr
Received: September 16, 2025
Revised: October 1, 2025
Accepted: November 5, 2025
Published online: November 26, 2025
Processing time: 71 Days and 13.7 Hours
Revised: October 1, 2025
Accepted: November 5, 2025
Published online: November 26, 2025
Processing time: 71 Days and 13.7 Hours
Core Tip
Core Tip: This study identifies GrpE-like 1 (GRPEL1) as a mitophagy-related biomarker that is suppressed in osteoarthritis and demonstrates that exosomes derived from synovial mesenchymal stem cells can be engineered to deliver GRPEL1 to chondrocytes. Delivery of GRPEL1 via these exosomes restores mitochondrial homeostasis through PINK1-dependent mitophagy, reduces oxidative damage, preserves the extracellular matrix, and improves histological outcomes in a rat model of osteoarthritis. This represents a translationally promising, cell-free strategy for disease modification in osteoarthritis.