Bone marrow mesenchymal stromal cell-derived exosomes in knee osteoarthritis: Bridging mechanistic understanding to clinical applications

doi:10.4252/wjsc.v18.i5.117689

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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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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Stem Cells. May 26, 2026; 18(5): 117689
Published online May 26, 2026. doi: 10.4252/wjsc.v18.i5.117689

Bone marrow mesenchymal stromal cell-derived exosomes in knee osteoarthritis: Bridging mechanistic understanding to clinical applications

Ashwini Raja, Naveen Jeyaraman, Ashika Mudilikulam Sukumaran, Aadithya Siddarth Sridhar, Swaminathan Ramasubramanian, Arulkumar Nallakumarasamy, Sathish Muthu, Madhan Jeyaraman

Ashwini Raja, Aadithya Siddarth Sridhar, Department of Orthopaedics, Faculty of Medicine - Sri Lalithambigai Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600095, Tamil Nadu, India

Naveen Jeyaraman, Madhan Jeyaraman, Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India

Naveen Jeyaraman, Swaminathan Ramasubramanian, Arulkumar Nallakumarasamy, Sathish Muthu, Madhan Jeyaraman, Department of Regenerative Medicine, Agathisha Institute of Stemcell and Regenerative Medicine, Chennai 600030, Tamil Nadu, India

Naveen Jeyaraman, Sathish Muthu, Madhan Jeyaraman, Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India

Ashika Mudilikulam Sukumaran, Department of Biochemistry, Faculty of Medicine - Sri Lalithambigai Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600095, Tamil Nadu, India

Arulkumar Nallakumarasamy, Department of Orthopaedics, Jawaharlal Institute of Postgraduate Medical Education and Research, Karaikal 609602, Puducherry, India

Sathish Muthu, Central Research Laboratory, Meenakshi Medical College Hospital and Research Institute, Meenakshi Academy of Higher Education and Research, Kanchipuram 631552, Tamil Nadu, India

Co-first authors: Ashwini Raja and Naveen Jeyaraman.

Author contributions: Raja A and Jeyaraman N contributed equally and are co-first authors. Jeyaraman N designed the research; Raja A, Jeyaraman N, Sukumaran AM, Sridhar AS, Ramasubramanian S, and Nallakumarasamy A analyzed the articles for performing review and wrote the manuscript; Muthu S and Jeyaraman M finalized the manuscript.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Corresponding author: Madhan Jeyaraman, MD, PhD, Researcher, Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Velappanchavadi, Chennai 600077, Tamil Nadu, India. madhanjeyaraman@gmail.com

Received: December 15, 2025
Revised: January 27, 2026
Accepted: March 3, 2026
Published online: May 26, 2026
Processing time: 163 Days and 14.4 Hours

Abstract

Knee osteoarthritis is recognised as a whole-joint disorder involving cartilage, synovium, subchondral bone and nociceptive pathways. Conventional therapies provide symptomatic relief but rarely alter structural progression. Mesenchymal stromal cell (MSC) injections improve pain and function, yet structural benefits remain modest and variable. Increasing evidence indicates that much of the MSC effect is mediated by secreted extracellular vesicles (EVs), particularly those derived from bone marrow MSCs. These vesicles deliver proteins, lipids, microRNAs and long noncoding RNAs that regulate catabolic enzymes, inflammatory mediators and survival pathways, thereby influencing chondrocyte apoptosis, matrix turnover, macrophage polarisation, osteoclast activity and nociceptive signalling. This review uniquely synthesises mechanistic insights into extracellular vesicles derived from bone marrow MSCs cargo, compares their performance with other MSC sources, and highlights translational priorities including Minimal Information for Studies of EVs 2023-compliant characterisation, dose-finding, and adequately powered trials with structural and biomarker endpoints.

Keywords: Knee osteoarthritis; Bone marrow; Mesenchymal stromal cells; Extracellular vesicles; Exosomes; Hydrogels

Core Tip: Bone marrow mesenchymal stromal cell exosomes show promise as cell-free therapeutics for knee osteoarthritis by delivering microRNAs and long noncoding RNAs that modulate nuclear factor kappa B, Wnt/β-catenin, phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin and mitogen-activated protein kinases pathways. They suppress chondrocyte apoptosis, enhance matrix synthesis, polarise macrophages, and reduce pain behaviours. Delivery innovations like hydrogels improve retention, but rigorous Minimal Information for Studies of Extracellular Vesicles 2023-compliant characterisation and adequately powered randomised trials remain essential before clinical translation as disease-modifying therapy.