Mesenchymal stem cell-derived exosomes: a new therapeutic approach to osteoarthritis?
Open accessAbstract
Degenerative disorders of joints, especially osteoarthritis (OA), result in persistent pain and disability and high costs to society. Nevertheless, the molecular mechanisms of OA have not yet been fully explained. OA is characterized by destruction of cartilage and loss of extracellular matrix (ECM). It is generally agreed that there is an association between pro-inflammatory cytokines and the development of OA. There is increased expression of matrix metalloproteinase (MMP) and “a disintegrin and metalloproteinase with thrombospondin motifs” (ADAMTS). Mesenchymal stem cells (MSCs) have been explored as a new treatment for OA during the last decade. It has been suggested that paracrine secretion of trophic factors, in which exosomes have a crucial role, contributes to the mechanism of MSC-based treatment of OA. The paracrine secretion of exosomes may play a role in the repair of joint tissue as well as MSC-based treatments for other disorders. Exosomes isolated from various stem cells may contribute to tissue regeneration in the heart, limbs, skin, and other tissues. Recent studies have indicated that exosomes (or similar particles) derived from MSCs may suppress OA development. Herein, for first time, we summarize the recent findings of studies on various exosomes derived from MSCs and their effectiveness in the treatment of OA. Moreover, we highlight the likely mechanisms of actions of exosomes in OA.
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Variability in MSC sources (bone marrow-derived, adipose-derived, umbilical cord-derived) contributes to discrepancies in reported outcomes.
“Furthermore, variability in MSC sources, such as bone marrow-derived (BM-MSCs), adipose-derived (AD-MSCs), and umbilical cord-derived MSCs (UC-MSCs), contributes to discrepancies in reported outcomes.”
From Advancements in Regenerative Therapies for Orthopedics: A Comprehensive Review of Platelet-Rich Plasma, Mesenchymal Stem Cells, Peptide Therapies, and Biomimetic Applications (2025) · cites this paper as [112]
In “Therapeutic potentials of MSC-derived exosomes from different cell origins in OA” (page unavailable), the review says MSC source can affect exosome composition and may profoundly affect therapeutic outcomes. It does not establish that differences among bone marrow-, adipose-, and umbilical cord-derived MSCs caused discrepancies in reported outcomes; the Introduction discusses umbilical cord-derived MSCs separately. (LLM, conf=0.85)
Experimental — accuracy not yet measuredMSC trials show variable results: some demonstrated substantial cartilage repair and functional improvement, while others reported minimal to no long-term benefit, particularly in advanced osteoarthritis.
“While some trials have demonstrated substantial cartilage repair and functional improvement, others have reported minimal to no long-term benefit, particularly in advanced osteoarthritis patients [112].”
From Advancements in Regenerative Therapies for Orthopedics: A Comprehensive Review of Platelet-Rich Plasma, Mesenchymal Stem Cells, Peptide Therapies, and Biomimetic Applications (2025) · cites this paper as [112]
The Introduction reports improved physical functioning and signs of cartilage regeneration at 12 months in an MSC trial. The “MSC-derived exosomes and OA” section also reports improved joint performance and cartilage repair in trials. Neither passage reports trials with minimal or no long-term benefit, particularly among patients with advanced osteoarthritis. (LLM, conf=0.89)
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- Authors
- Mianehsaz, E., Mirzaei, H. R., Mahjoubin-Tehran, M., Rezaee, A., Sahebnasagh, R., Pourhanifeh, M. H., Mirzaei, H., & Hamblin, M. R.
- Affiliations
- Kashan University of Medical Sciences (IR)
- Tehran University of Medical Sciences (IR)
- Harvard University (US)
- Corresponding author
- Mirzaei, Hamid Reza
- Mirzaei, Hamed
- Hamblin, Michael R.
- ORCID
- Venue
- Stem Cell Research & Therapy
- Published
- 2019-11-21
- Volume
- 10
- Issue
- 1
- Pages
- 340-340
- ISSN
- 1757-6512 (ISSN-L)
- PMC
- PMC6873475
- OpenAlex
- W2990542915
- Cited by
- 274
- References
- 126
- Citations by year
- 2026: 15 · 2025: 28 · 2024: 35 · 2023: 44 · 2022: 45 · 2021: 74 · 2020: 33
- FWCI
- 6.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Stem Cell Research & Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI050875, R21AI121700)
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- mesenchymal stem cells, exosomes, osteoarthritis, cartilage degeneration, extracellular matrix, paracrine signaling, matrix metalloproteinases, ADAMTS, inflammatory cytokines, tissue regeneration, stem cell therapy
- MeSH terms
- Animals, Humans, Osteoarthritis, Exosomes, Mesenchymal Stem Cells
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