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Frontiers in cell and developmental biology2026; 14; 1763344; doi: 10.3389/fcell.2026.1763344

Multiple strategies, one mission: mesenchymal stromal cell-based mechanisms of action in osteoarthritis.

Abstract: Osteoarthritis (OA) is a cross-species, multifactorial joint disease characterized by the progressive degeneration of articular cartilage, morphological remodeling of the subchondral bone, and inflammatory and fibrotic changes of the joint capsule. These alterations arise from chronic, often subclinical, inflammatory processes and dysregulated cellular homeostasis, leading to profound shifts in the cellular and extracellular composition of the joint organ. Although the mechanisms driving persistent inflammation are only partially understood, their impact on all joint-associated tissues is well-established. Mesenchymal stromal cells (MSCs) have gained increasing attention as therapeutic candidates for OA due to their immunomodulatory and potentially regenerative capacities. Increasing evidence indicates that MSCs exert their effects predominantly through indirect mechanisms, including paracrine signaling, the release of extracellular vesicles, mitochondrial transfer, and modulation of innate and adaptive immune responses. This review summarizes current insights into how these mechanisms may act within the articular microenvironment to attenuate cartilage degeneration and promote tissue repair in OA. Herein, we consider the effects of MSCs on different cell types and tissues within the joint, and highlight mitochondrial transfer as an emerging mechanism through which MSCs may regenerate and protect them, thereby contributing to the rescue of joint homeostasis.
Copyright © 2026 Junuzović, Troillet and Burk.
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Publication Date: 2026-04-20 PubMed ID: 42089113PubMed Central: PMC13136253DOI: 10.3389/fcell.2026.1763344Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

Introduction to Osteoarthritis (OA)

  • OA is a complex, degenerative joint disease affecting multiple species.
  • Key features include progressive cartilage breakdown, changes in subchondral bone structure, and inflammatory and fibrotic changes in the joint capsule.
  • The disease is driven by chronic and often subclinical inflammatory processes disrupting normal cellular balance (homeostasis).
  • These pathological processes alter the cellular and extracellular environment of the entire joint organ.
  • The specific mechanisms underlying persistent joint inflammation in OA are still only partially understood, but their wide-reaching impact is clear.

Role of Mesenchymal Stromal Cells (MSCs) in OA

  • MSCs are multipotent cells known for their ability to modulate immune responses and potentially regenerate damaged tissue, making them promising candidates for OA therapy.
  • The therapeutic effects of MSCs are primarily indirect rather than through direct engraftment and tissue replacement.
  • These effects include multiple mechanisms:
    • Paracrine signaling: MSCs release soluble factors that influence neighboring cells and tissues to reduce inflammation and support repair.
    • Release of extracellular vesicles: Small membrane-bound particles that carry proteins, RNA, and other molecules to recipient cells, modulating their behavior.
    • Mitochondrial transfer: MSCs can donate mitochondria to damaged or stressed cells, supporting their energy metabolism and survival.
    • Modulation of both innate and adaptive immune system components, reducing harmful inflammation in the joint microenvironment.

Mechanistic Insights Within the Joint Microenvironment

  • MSC actions target various joint cell types and tissues impacted by OA, including:
    • Chondrocytes (cartilage cells), which are protected and stimulated to resist degeneration.
    • Synovial cells and immune cells, whose inflammatory activity is modulated to a less damaging state.
    • Subchondral bone cells, where remodeling processes are influenced.
  • MSC-derived mitochondrial transfer is highlighted as an emerging and important mechanism supporting cellular energy demands and possible repair processes.
  • Collectively, these mechanisms help restore joint homeostasis by reducing inflammation, preventing further cartilage breakdown, and promoting regenerative processes.

Conclusion and Implications

  • The article synthesizes existing research suggesting that MSC-based therapies do not rely on a single mode of action but instead employ multiple complementary strategies to combat OA pathology.
  • Understanding these varied mechanisms is critical to optimizing MSC therapy protocols and maximizing clinical benefits.
  • Further research is needed to fully characterize and harness these mechanisms, particularly mitochondrial transfer, in clinical OA treatment.

Cite This Article

APA
Junuzović M, Troillet A, Burk J. (2026). Multiple strategies, one mission: mesenchymal stromal cell-based mechanisms of action in osteoarthritis. Front Cell Dev Biol, 14, 1763344. https://doi.org/10.3389/fcell.2026.1763344

Publication

Frontiers in cell and developmental biology
ISSN: 2296-634X
NlmUniqueID: 101630250
Country: Switzerland
Language: English
Volume: 14
Pages: 1763344
PII: 1763344

Researcher Affiliations

Junuzović, Maid
  • Physiology and Pathophysiology, Department of Biological Sciences and Pathobiology, University of Veterinary Medicine Vienna, Vienna, Austria.
Troillet, Antonia
  • Department for Horses, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany.
Burk, Janina
  • Physiology and Pathophysiology, Department of Biological Sciences and Pathobiology, University of Veterinary Medicine Vienna, Vienna, Austria.

Conflict of Interest Statement

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

This article includes 188 references
  1. Abramson SB, Attur M. Developments in the scientific understanding of osteoarthritis. Arthritis Res. Ther. 11 (3), 227.
    doi: 10.1186/ar2655pmc: PMC2714096pubmed: 19519925google scholar: lookup
  2. Ahmad T, Mukherjee S, Pattnaik BR, Kumar M, Singh S, Rehman R. Miro 1 knockdown in stem cells inhibits mitochondrial donation mediated rescue of bronchial epithelial injury. Biophys. J. 104, 659a.
    doi: 10.1016/j.bpj.2012.11.3638google scholar: lookup
  3. Ahmed MR, Mehmood A, Bhatti F-R, Khan SN, Riazuddin S. Combination of ADMSCs and chondrocytes reduces hypertrophy and improves the functional properties of osteoarthritic cartilage. OAC 22, 1894–1901.
    doi: 10.1016/j.joca.2014.07.028pubmed: 25128628google scholar: lookup
  4. Ahmed HA, Elhossini R, Aglan M, Amr K. Aggrecan-related bone disorders; a novel heterozygous ACAN variant associated with spondyloepimetaphyseal dysplasia expanding the phenotypic spectrum and review of literature. J. Genet. Eng. and Biotechnol. 22, 100341.
    doi: 10.1016/j.jgeb.2023.100341pmc: PMC10860877pubmed: 38494255google scholar: lookup
  5. Altaie A, Baboolal T, Wall O, Ananad S, Rowbotham E, Pandit H. Preliminary evidence that synovial membrane mesenchymal stem cell mobilisation intraoperatively with novel stem cell-mobilizing device may facilitate joint repair post microfracture surgery. OAC 32, S272.
    doi: 10.1016/j.joca.2024.02.391google scholar: lookup
  6. Andreu JL, Trujillo A, Alonso JM, Mulero J, Martínez C. Selective expansion of T cells bearing the gamma/delta receptor and expressing an unusual repertoire in the synovial membrane of patients with rheumatoid arthritis. Arthritis Rheum. 34 (7), 808–814.
    doi: 10.1002/art.1780340705pubmed: 1829358google scholar: lookup
  7. Araya-Sapag MJ, Lara-Barba E, García-Guerrero C, Herrera-Luna Y, Flores-Elías Y, Bustamante-Barrientos FA. New mesenchymal stem/stromal cell-based strategies for osteoarthritis treatment: targeting macrophage-mediated inflammation to restore joint homeostasis. J. Mol. Med. Berl. 103, 651–669.
    doi: 10.1007/s00109-025-02547-8pubmed: 40272537google scholar: lookup
  8. Armiento AR, Alini M, Stoddart MJ. Articular fibrocartilage - why does hyaline cartilage fail to repair?. Adv. Drug Deliv. Rev. 146, 289–305.
    doi: 10.1016/j.addr.2018.12.015pubmed: 30605736google scholar: lookup
  9. Austefjord MW, Gerdes H-H, Wang X. Tunneling nanotubes: diversity in morphology and structure. Commun. Integr. Biol. 7, e27934.
    doi: 10.4161/cib.27934pmc: PMC3995728pubmed: 24778759google scholar: lookup
  10. Barbash IM, Chouraqui P, Baron J, Feinberg MS, Etzion S, Tessone A. Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circ 108, 863–868.
    doi: 10.1161/01.CIR.0000084828.50310.6Apubmed: 12900340google scholar: lookup
  11. Barry F. MSC therapy for osteoarthritis: an unfinished story. J. Orthop. Res. 37, 1229–1235.
    doi: 10.1002/jor.24343pubmed: 31081558google scholar: lookup
  12. Bartok B, Firestein GS. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol. Rev. 233 (1), 233–255.
    doi: 10.1111/j.0105-2896.2009.00859.xpmc: PMC2913689pubmed: 20193003google scholar: lookup
  13. Basheer WA, Xiao S, Epifantseva I, Fu Y, Kleber AG, Hong T. GJA1-20k arranges actin to guide Cx43 delivery to cardiac intercalated discs. Circ. Res. 121, 1069–1080.
    doi: 10.1161/CIRCRESAHA.117.311955pmc: PMC5790189pubmed: 28923791google scholar: lookup
  14. Benjamin M, Ralphs JR. Biology of fibrocartilage cells. Int. Rev. Cytol. 233, 1–45.
    doi: 10.1016/S0074-7696(04)33001-9pubmed: 15037361google scholar: lookup
  15. Bennett MP, Vivancos-Koopman I, Seewald L, Wells K, Robinette T, Delco ML. Intercellular mitochondrial transfer from mesenchymal stem cells to stressed chondrocytes. OAC 27, S51–S52.
    doi: 10.1016/j.joca.2019.02.074google scholar: lookup
  16. Bok E.-Y., Lee W.-J., Lee H., Jo C.-H., Hong C.-Y., Kang S.-Y.. Immunomodulatory, anti-synoviocyte, and anti-osteoclastic abilities of embryonic stem cell-derived mesenchymal stem cells in rheumatoid arthritis. Exp. Cell Res. 450, 114660.
    doi: 10.1016/j.yexcr.2025.114660pubmed: 40582583google scholar: lookup
  17. Boltze J., Arnold A., Walczak P., Jolkkonen J., Cui L., Wagner D.-C.. The dark side of the force - constraints and complications of cell therapies for stroke. Front. Neurol. 6, 155.
    doi: 10.3389/fneur.2015.00155pmc: PMC4507146pubmed: 26257702google scholar: lookup
  18. Brennan F. M., McInnes I. B.. Evidence that cytokines play a role in rheumatoid arthritis. J. Clin. Invest. 118, 3537–3545.
    doi: 10.1172/JCI36389pmc: PMC2575731pubmed: 18982160google scholar: lookup
  19. Brody L. T.. Knee osteoarthritis: clinical connections to articular cartilage structure and function. Phys. Ther. Sport 16, 301–316.
    doi: 10.1016/j.ptsp.2014.12.001pubmed: 25783021google scholar: lookup
  20. Bronckaers A., Hilkens P., Martens W., Gervois P., Ratajczak J., Struys T.. Mesenchymal stem/stromal cells as a pharmacological and therapeutic approach to accelerate angiogenesis. Pharmacol. Ther. 143, 181–196.
    doi: 10.1016/j.pharmthera.2014.02.013pubmed: 24594234google scholar: lookup
  21. Burk J., Berner D., Brehm W., Hillmann A., Horstmeier C., Josten C.. Long-term cell tracking following local injection of mesenchymal stromal cells in the equine model of induced tendon disease. Cell Transpl. 25, 2199–2211.
    doi: 10.3727/096368916X692104pubmed: 27392888google scholar: lookup
  22. Burk J., Glauche S. M., Brehm W., Crovace A., Francioso E., Hillmann A.. Characterisation and intracellular labelling of mesenchymal stromal cells derived from synovial fluid of horses and sheep. Vet. J. 222, 1–8.
    doi: 10.1016/j.tvjl.2017.02.006pubmed: 28410670google scholar: lookup
  23. Burk J., Sassmann A., Kasper C., Nimptsch A., Schubert S.. Extracellular matrix synthesis and remodeling by mesenchymal stromal cells is context-sensitive. Int. J. Mol. Sci. 23, 1758.
    doi: 10.3390/ijms23031758pmc: PMC8836208pubmed: 35163683google scholar: lookup
  24. Caplan A. I.. Why are MSCs therapeutic? New data: new insight. J. Pathology 217, 318–324.
    doi: 10.1002/path.2469pmc: PMC8793150pubmed: 19023885google scholar: lookup
  25. Caplan A. I.. Mesenchymal stem cells: time to change the name. Stem Cells Transl. Med. 6, 1445–1451.
    doi: 10.1002/sctm.17-0051pmc: PMC5689741pubmed: 28452204google scholar: lookup
  26. Caplan A. I., Correa D.. The MSC: an injury drugstore. Cell Stem Cell 9, 11–15.
    doi: 10.1016/j.stem.2011.06.008pmc: PMC3144500pubmed: 21726829google scholar: lookup
  27. Castrogiovanni P., Di Rosa M., Ravalli S., Castorina A., Guglielmino C., Imbesi R.. Moderate physical activity as a prevention method for knee osteoarthritis and the role of synoviocytes as biological key. Int. J. Mol. Sci. 20 (3), 511.
    doi: 10.3390/ijms20030511pmc: PMC6387266pubmed: 30691048google scholar: lookup
  28. Chang S. K., Gu Z., Brenner M. B.. Fibroblast-like synoviocytes in inflammatory arthritis pathology: the emerging role of cadherin-11. Immunol. Rev. 233, 256–266.
    doi: 10.1111/j.0105-2896.2009.00854.xpubmed: 20193004google scholar: lookup
  29. Chen W., Sun Y., Gu X., Hao Y., Liu X., Lin J.. Conditioned medium of mesenchymal stem cells delays osteoarthritis progression in a rat model by protecting subchondral bone, maintaining matrix homeostasis, and enhancing autophagy. J. Tissue Eng. Regen. Med. 13, 1618–1628.
    doi: 10.1002/term.2916pubmed: 31210406google scholar: lookup
  30. Chen Z., Pang Q., Zhan J., Liu J., Zhao W., Dong L.. MSCs-derived ECM functionalized hydrogel regulates macrophage reprogramming for osteoarthritis treatment by improving mitochondrial function and energy metabolism. Mater. Today bio. 29, 101340.
    doi: 10.1016/j.mtbio.2024.101340pmc: PMC11617891pubmed: 39640869google scholar: lookup
  31. Chen M, Liu Y, Cao Y, Zhao C, Liu Q, Li N. Remodeling the proinflammatory microenvironment in osteoarthritis through Interleukin-1 beta tailored exosome cargo for inflammatory regulation and cartilage regeneration. ACS Nano 19, 4924–4941.
    doi: 10.1021/acsnano.4c16785pubmed: 39848926google scholar: lookup
  32. Chi P-L, Cheng C-C, Hung C-C, Wang M-T, Liu H-Y, Ke M-W. MMP-10 from M1 macrophages promotes pulmonary vascular remodeling and pulmonary arterial hypertension. Int. J. Biol. Sci. 18, 331–348.
    doi: 10.7150/ijbs.66472pmc: PMC8692144pubmed: 34975336google scholar: lookup
  33. Chou C-H, Jain V, Gibson J, Attarian D E, Haraden C A, Yohn C B. Synovial cell cross-talk with cartilage plays a major role in the pathogenesis of osteoarthritis. Sci. Rep. 10, 10868.
    doi: 10.1038/s41598-020-67730-ypmc: PMC7331607pubmed: 32616761google scholar: lookup
  34. Court A C, Vega-Letter A M, Parra-Crisóstomo E, Velarde F, García C, Ortloff A. Mitochondrial transfer balances cell redox, energy and metabolic homeostasis in the osteoarthritic chondrocyte preserving cartilage integrity. Theranostics 14 (17), 6471–6486.
    doi: 10.7150/thno.96723pmc: PMC11519804pubmed: 39479450google scholar: lookup
  35. Cowman M K, Lee H-G, Schwertfeger K L, McCarthy J B, Turley E A. The content and size of hyaluronan in biological fluids and tissues. Front. Immunol. 6, 261.
    doi: 10.3389/fimmu.2015.00261pmc: PMC4451640pubmed: 26082778google scholar: lookup
  36. Croucher L J, Crawford A, Hatton P V, Russell R G, Buttle D J. Extracellular ATP and UTP stimulate cartilage proteoglycan and collagen accumulation in bovine articular chondrocyte pellet cultures. Biochim. Biophys. Acta 18 (2), 297–306.
    doi: 10.1016/s0925-4439(00)00055-7pubmed: 11040454google scholar: lookup
  37. Cui L L, Kerkelä E, Bakreen A, Nitzsche F, Andrzejewska A, Nowakowski A. The cerebral embolism evoked by intra-arterial delivery of allogeneic bone marrow mesenchymal stem cells in rats is related to cell dose and infusion velocity. Stem Cell Res. Ther. 27 (1), 11.
    doi: 10.1186/scrt544pmc: PMC4429328pubmed: 25971703google scholar: lookup
  38. Culemann S, Grüneboom A, Nicolás-Ávila J Á, Weidner D, Lämmle K F, Rothe T. Locally renewing resident synovial macrophages provide a protective barrier for the joint. Nat 572, 670–675.
    doi: 10.1038/s41586-019-1471-1pmc: PMC6805223pubmed: 31391580google scholar: lookup
  39. Damerau A, Kirchner M, Pfeiffenberger M, Ehlers L, Do Nguyen D H, Mertins P. Metabolic reprogramming of synovial fibroblasts in osteoarthritis by inhibition of pathologically overexpressed pyruvate dehydrogenase kinases. Metab. Eng. 72, 116–132.
    doi: 10.1016/j.ymben.2022.03.006pubmed: 35296430google scholar: lookup
  40. Davis C O, Kim K-Y, Bushong E A, Mills E A, Boassa D, Shih T. Transcellular degradation of axonal mitochondria. Proc. Natl. Acad. Sci. USA. 111, 9633–9638.
    doi: 10.1073/pnas.1404651111pmc: PMC4084443pubmed: 24979790google scholar: lookup
  41. De Bari C, Dell'Accio F, Tylzanowski P, Luyten F P. Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum. 44 (8), 1928–1942.
    doi: 10.1002/1529-0131(200108)44:8<1928::AID-ART331>3.0pubmed: 11508446google scholar: lookup
  42. De Luca P, Kouroupis D, Viganò M, Perucca-Orfei C, Kaplan L, Zagra L. Human diseased articular cartilage contains a mesenchymal stem cell-like population of chondroprogenitors with strong immunomodulatory responses. J. Clin. Med. 28 (4), 423.
    doi: 10.3390/jcm8040423pmc: PMC6517884pubmed: 30925656google scholar: lookup
  43. Delco M L, Bonnevie E D, Bonassar L J, Fortier L A. Mitochondrial dysfunction is an acute response of articular chondrocytes to mechanical injury. J. Orthop. Res. 36, 739–750.
    doi: 10.1002/jor.23651pmc: PMC5764818pubmed: 28696002google scholar: lookup
  44. Devine S M, Cobbs C, Jennings M, Bartholomew A, Hoffman R. Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman Primates. Blood 101, 2999–3001.
    doi: 10.1182/blood-2002-06-1830pubmed: 12480709google scholar: lookup
  45. Di Lullo G A, Sweeney S M, Korkko J, Ala-Kokko L, San Antonio J D. Mapping the ligand-binding sites and disease-associated mutations on the most abundant protein in the human, type I collagen. J. Biological Chemistry 277, 4223–4231.
    doi: 10.1074/jbc.M110709200pubmed: 11704682google scholar: lookup
  46. DiBartola AC, Everhart JS, Magnussen RA, Carey JL, Brophy RH, Schmitt LC. Correlation between histological outcome and surgical cartilage repair technique in the knee: a meta-analysis. Knee 23, 344–349.
    doi: 10.1016/j.knee.2016.01.017pubmed: 26898766google scholar: lookup
  47. Ding M, Cheng Y, Xu Z, Lu Y, Li J, Lu L. Hypoxia inhibits osteogenesis and promotes adipogenesis of fibroblast-like synoviocytes upregulation of leptin in patients with rheumatoid arthritis. J. Immunol. Res. 2022, 1431399.
    doi: 10.1155/2022/1431399pmc: PMC9750767pubmed: 36530571google scholar: lookup
  48. Doll CU, Niebert S, Burk J. Mesenchymal stromal cells adapt to chronic tendon disease environment with an initial reduction in matrix remodeling. Int. J. Mol. Sci. 22, 12798.
    doi: 10.3390/ijms222312798pmc: PMC8657831pubmed: 34884602google scholar: lookup
  49. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D. Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy 8, 315–317.
    doi: 10.1080/14653240600855905pubmed: 16923606google scholar: lookup
  50. Du Z, Wei C, Yan J, Han B, Zhang M, Peng C. Mesenchymal stem cells overexpressing C-X-C chemokine receptor type 4 improve early liver regeneration of small-for-size liver grafts. Liver. Transpl. 19, 215–225.
    doi: 10.1002/lt.23577pubmed: 23193024google scholar: lookup
  51. Durán-Sotuela A, Oreiro N, Fernández-Moreno M, Vázquez-García J, Relaño-Fernández S, Balboa-Barreiro V. Mitonuclear epistasis involving TP63 and haplogroup Uk: risk of rapid progression of knee OA in patients from the OAI. Osteoarthr. Cartil. 32 (5), 526–534.
    doi: 10.1016/j.joca.2023.12.008pubmed: 38190960google scholar: lookup
  52. Edwards JC. The nature and origins of synovium: experimental approaches to the study of synoviocyte differentiation. J. Anat. 184 (Pt 3), 493–501.
    pmc: PMC1259957pubmed: 7928638
  53. Endo K, Horiuchi K, Katano H, Ozeki N, Sakamaki Y, Koga H. Intra-articular injection of PDGF-BB explored in a novel model mobilizes mesenchymal stem cells from the synovium into synovial fluid in rats. Stem Cell Rep. 17, 1768–1779.
    doi: 10.1007/s12015-021-10156-4pubmed: 33772387google scholar: lookup
  54. Estell EG, Silverstein AM, Stefani RM, Lee AJ, Murphy LA, Shah RP. Cartilage wear particles induce an inflammatory response similar to cytokines in human fibroblast-like synoviocytes. J. Orthop. Res. 37, 1979–1987.
    doi: 10.1002/jor.24340pmc: PMC6834361pubmed: 31062877google scholar: lookup
  55. Fahey M, Bennett M, Thomas M, Montney K, Vivancos-Koopman I, Pugliese B. Mesenchymal stromal cells donate mitochondria to articular chondrocytes exposed to mitochondrial, environmental, and mechanical stress. Sci. Rep. 12, 21525.
    doi: 10.1038/s41598-022-25844-5pmc: PMC9747781pubmed: 36513773google scholar: lookup
  56. Fahy N, Vries-van Melle ML, Lehmann J, Wei W, Grotenhuis N, Farrell E. Human osteoarthritic synovium impacts chondrogenic differentiation of mesenchymal stem cells macrophage polarisation state. OAC 22, 1167–1175.
    doi: 10.1016/j.joca.2014.05.021pubmed: 24911520google scholar: lookup
  57. Fernandez-Pernas P, Rodríguez-Lesende I, La Fuente A, Mateos J, Fuentes I, Toro J. CD105+-mesenchymal stem cells migrate into osteoarthritis joint: an animal model. PloS One 12, e0188072.
    doi: 10.1371/journal.pone.0188072pmc: PMC5708708pubmed: 29190645google scholar: lookup
  58. Fischer UM, Harting MT, Jimenez F, Monzon-Posadas WO, Xue H, Savitz SI. Pulmonary passage is a major obstacle for intravenous stem cell delivery: the pulmonary first-pass effect. Stem Cell Dev. 18, 683–692.
    doi: 10.1089/scd.2008.0253pmc: PMC3190292pubmed: 19099374google scholar: lookup
  59. Fong CY, Subramanian A, Biswas A, Bongso A. Freezing of fresh wharton's jelly from human umbilical cords yields high post-thaw mesenchymal stem cell numbers for cell-based therapies. J. Cell. Biochem. 117, 815–827.
    doi: 10.1002/jcb.25375pubmed: 26365815google scholar: lookup
  60. Fontaine MJ, Shih H, Schäfer R, Pittenger MF. Unraveling the mesenchymal stromal cells' paracrine immunomodulatory effects. Transfus. Med. Rev. 30, 37–43.
    doi: 10.1016/j.tmrv.2015.11.004pubmed: 26689863google scholar: lookup
  61. Fu Y, Karbaat L, Wu L, Leijten J, Both S K, Karperien M. Trophic effects of mesenchymal stem cells in tissue regeneration. Tissue Eng. Part B Rev. 23, 515–528.
    doi: 10.1089/ten.teb.2016.0365pubmed: 28490258google scholar: lookup
  62. Fülber J, Maria D A, Da Silva L C L C, Massoco C O, Agreste F, Baccarin R Y A. Comparative study of equine mesenchymal stem cells from healthy and injured synovial tissues: an assessment. Stem Cell Res. Ther. 7, 35.
    doi: 10.1186/s13287-016-0294-3pmc: PMC4779201pubmed: 26944403google scholar: lookup
  63. Furman B D, Kimmerling K A, Zura R D, Reilly R M, Zlowodzki M P, Huebner J L. Articular ankle fracture results in increased synovitis, synovial macrophage infiltration, and synovial fluid concentrations of inflammatory cytokines and chemokines. Arthritis Rheumatol. 67, 1234–1239.
    doi: 10.1002/art.39064pmc: PMC4819001pubmed: 25707992google scholar: lookup
  64. Gao J, Dennis J E, Muzic R F, Lundberg M, Caplan A I. The dynamic distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs 169 (1), 12–20.
    doi: 10.1159/000047856pubmed: 11340257google scholar: lookup
  65. Garcia J, Mennan C, McCarthy H S, Roberts S, Richardson J B, Wright K T. Chondrogenic potency analyses of donor-matched chondrocytes and mesenchymal stem cells derived from bone marrow, infrapatellar fat pad, and subcutaneous fat. Stem Cells Int. 2016, 6969726.
    doi: 10.1155/2016/6969726pmc: PMC5066011pubmed: 27781068google scholar: lookup
  66. He Y, Wang X, Xu B, Chen S, Li H, Chang B. The potential of mitochondrial transfer as the modifying therapy for osteoarthritis. Front. Cell Dev. Biol. 13, 1643141.
    doi: 10.3389/fcell.2025.1643141pmc: PMC12417883pubmed: 40932934google scholar: lookup
  67. Heller W T, Vigil D, Brown S, Blumenthal D K, Taylor S S, Trewhella J. C subunits binding to the protein kinase A RI alpha dimer induce a large conformational change. J. Biol. Chem. 279, 19084–19090.
    doi: 10.1074/jbc.M313405200pubmed: 14985329google scholar: lookup
  68. Heywood H K, Knight M M, Lee D A. Both superficial and deep zone articular chondrocyte subpopulations exhibit the crabtree effect but have different basal oxygen consumption rates. J. Cell. Physiol. 223, 630–639.
    doi: 10.1002/jcp.22061pubmed: 20143333google scholar: lookup
  69. Holderness J, Hedges J F, Ramstead A, Jutila M A. Comparative biology of γδ T cell function in humans, mice, and domestic animals. Annu. Rev. Anim. Biosci. 1, 99–124.
    doi: 10.1146/annurev-animal-031412-103639pubmed: 25387013google scholar: lookup
  70. Honczarenko M, Glodek A M, Swierkowski M, Na I-K, Silberstein L E. Developmental stage-specific shift in responsiveness to chemokines during human B-cell development. Exp. Hematol. 34, 1093–1100.
    doi: 10.1016/j.exphem.2006.05.013pubmed: 16863916google scholar: lookup
  71. Hou S-M, Chen P-C, Lin C-M, Fang M-L, Chi M-C, Liu J-F. CXCL1 contributes to IL-6 expression in osteoarthritis and rheumatoid arthritis synovial fibroblasts by CXCR2, c-Raf, MAPK, and AP-1 pathway. Arthritis Res. Ther. 22, 251.
    doi: 10.1186/s13075-020-02331-8pmc: PMC7580030pubmed: 33087182google scholar: lookup
  72. Hsu H-C, Chang W-M, Wu J-Y, Huang C-C, Lu F-J, Chuang Y-W. Folate deficiency triggered apoptosis of synoviocytes: role of overproduction of reactive oxygen species generated NADPH oxidase/mitochondrial complex II and calcium perturbation. PLoS One 11, e0146440.
    doi: 10.1371/journal.pone.0146440pmc: PMC4714898pubmed: 26771387google scholar: lookup
  73. Huang Z, Xiao Y, Chen X, Li H, Gao J, Wei W. Cotransplantation of umbilical cord mesenchymal stem cells promotes the engraftment of umbilical cord blood stem cells in iron overload NOD/SCID mice. Transpl. CELL Ther. 27, 230.e1–230.e7.
    doi: 10.1016/j.jtct.2020.12.003pubmed: 35348116google scholar: lookup
  74. Huňáková K, Hluchý M, Špaková T, Matejová J, Mudroňová D, Kuricová M. Study of bilateral elbow joint osteoarthritis treatment using conditioned medium from allogeneic adipose tissue-derived MSCs in labrador retrievers. Res. Vet. Sci. 132, 513–520.
    doi: 10.1016/j.rvsc.2020.08.004pubmed: 32805699google scholar: lookup
  75. Im G-I. Tissue engineering in osteoarthritis: current status and prospect of mesenchymal stem cell therapy. BioDrugs 32, 183–192.
    doi: 10.1007/s40259-018-0276-3pubmed: 29704190google scholar: lookup
  76. Irwin RM, Thomas MA, Fahey MJ, Mayán MD, Smyth JW, Delco ML. Connexin 43 regulates intercellular mitochondrial transfer from human mesenchymal stromal cells to chondrocytes.. Stem Cell Res. Ther. 15, 359.
    doi: 10.1186/s13287-024-03932-9pmc: PMC11468299pubmed: 39390589google scholar: lookup
  77. Islam MN, Das SR, Emin MT, Wei M, Sun L, Westphalen K. Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury.. Nat. Med. 18, 759–765.
    doi: 10.1038/nm.2736pmc: PMC3727429pubmed: 22504485google scholar: lookup
  78. Ivanovska A, Mancuso P, Burke A, Hennessy C, Raman S, Dooley C. Identification of disease-stage therapeutic responses of mesenchymal stromal cells retrieved from murine osteoarthritic joints.. Front. Cell Dev. Biol. 13, 1521437.
    doi: 10.3389/fcell.2025.1521437pmc: PMC11980424pubmed: 40206403google scholar: lookup
  79. Janicka K, Beldowski P, Majewski T, Urbaniak W, Petelska AD. The amphoteric and hydrophilic properties of cartilage surface in mammalian joints: interfacial tension and molecular dynamics simulation studies.. Molecules 24 (12), 2248.
    doi: 10.3390/molecules24122248pmc: PMC6630197pubmed: 31208115google scholar: lookup
  80. Jones EA, English A, Henshaw K, Kinsey SE, Markham AF, Emery P. Enumeration and phenotypic characterization of synovial fluid multipotential mesenchymal progenitor cells in inflammatory and degenerative arthritis.. Arthritis Rheum. 50, 817–827.
    doi: 10.1002/art.20203pubmed: 15022324google scholar: lookup
  81. Jones IA, Chen X, Evseenko D, Vangsness CT. Nomenclature inconsistency and selective outcome reporting hinder understanding of stem cell therapy for the knee.. J. Bone Jt. Surg. Am. 101, 186–195.
    doi: 10.2106/JBJS.17.01474pubmed: 30653050google scholar: lookup
  82. Jung W-H, Takeuchi R, Chun C-W, Lee J-S, Ha J-H, Kim J-H. Second-look arthroscopic assessment of cartilage regeneration after medial opening-wedge high tibial osteotomy.. Arthroscopy 30, 72–79.
    doi: 10.1016/j.arthro.2013.10.008pubmed: 24384273google scholar: lookup
  83. Kasper G, Glaeser JD, Geissler S, Ode A, Tuischer J, Matziolis G. Matrix metalloprotease activity is an essential link between mechanical stimulus and mesenchymal stem cell behavior.. Stem Cells 25, 1985–1994.
    doi: 10.1634/stemcells.2006-0676pubmed: 17495113google scholar: lookup
  84. Kim D, Song J, Jin E-J. BNIP3-Dependent mitophagy PGC1α promotes cartilage degradation.. Cells 10, 1839.
    doi: 10.3390/cells10071839pmc: PMC8304751pubmed: 34360007google scholar: lookup
  85. Korpershoek JV, Rikkers M, Wallis FSA, Dijkstra K, Te Raa M, Knijff P. Mitochondrial transport from mesenchymal stromal cells to chondrocytes increases DNA content and proteoglycan deposition in 3D cultures.. Cartilage 13, 133–147.
    doi: 10.1177/19476035221126346pmc: PMC9924973pubmed: 36262105google scholar: lookup
  86. Kraitchman DL, Tatsumi M, Gilson WD, Ishimori T, Kedziorek D, Walczak P. Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction.. Circulation 112, 1451–1461.
    doi: 10.1161/CIRCULATIONAHA.105.537480pmc: PMC1456731pubmed: 16129797google scholar: lookup
  87. Lamers K, Baquero M, Karrow N, Hurtig M. Intra-articular xenogeneic mesenchymal stem cell-based therapy increases CD4+CD25+ cells in synovial fluid.. Vet. Immunol. Immunopathol. 227, 110085.
    doi: 10.1016/j.vetimm.2020.110085pubmed: 32673892google scholar: lookup
  88. Le Blanc K, Mougiakakos D. Multipotent mesenchymal stromal cells and the innate immune system.. Nat. Rev. Immunol. 12, 383–396.
    doi: 10.1038/nri3209pubmed: 22531326google scholar: lookup
  89. Lee H-J, Kim Y-H, Choi D-W, Cho K-A, Park J-W, Shin S-J. Tonsil-derived mesenchymal stem cells enhance allogeneic bone marrow engraftment via collagen IV degradation.. Stem Cell Res. Ther. 12, 329.
    doi: 10.1186/s13287-021-02414-6pmc: PMC8180137pubmed: 34090520google scholar: lookup
  90. Lee AR, Woo JS, Lee SY, Na HS, Cho KH, Lee YS. Mitochondrial transplantation ameliorates the development and progression of osteoarthritis.. Immune Netw. 21 (2), e14.
    doi: 10.4110/in.2022.22.e14pmc: PMC9066007pubmed: 35573148google scholar: lookup
  91. Lefebvre V, Dvir-Ginzberg M. SOX9 and the many facets of its regulation in the chondrocyte lineage.. Connect. Tissue Res. 58, 2–14.
    doi: 10.1080/03008207.2016.1183667pmc: PMC5287363pubmed: 27128146google scholar: lookup
  92. Li H, Wang D, Yuan Y, Min J. New insights on the MMP-13 regulatory network in the pathogenesis of early osteoarthritis.. Arthritis Res. Ther. 19, 248.
    doi: 10.1186/s13075-017-1454-2pmc: PMC5681770pubmed: 29126436google scholar: lookup
  93. Li M, Luo X, Long X, Jiang P, Jiang Q, Guo H. Potential role of mitochondria in synoviocytes.. Clin. Rheumatol. 40, 447–457.
    doi: 10.1007/s10067-020-05263-5pubmed: 32613391google scholar: lookup
  94. Li Y, Dong J, Zhou Y, Ye X, Cai Z, Zhang X. Therapeutic effects of CXCL9-overexpressing human umbilical cord mesenchymal stem cells on liver fibrosis in rats.. Biochem. Biophys. Res. Commun. 584, 87–94.
    doi: 10.1016/j.bbrc.2021.10.078pubmed: 34775285google scholar: lookup
  95. Li Y, Duan J, Lin W, Liu J. Exosomal miR-93-5p regulated the progression of osteoarthritis by targeting ADAMTS9.. Open Med. (Wars.) 18, 20230668.
    doi: 10.1515/med-2023-0668pmc: PMC10024348pubmed: 36941991google scholar: lookup
  96. Li X, Lu W, Ni L, Su J, Wang D, Deng Z. Mitochondria-rich extracellular vesicles derived from the culture supernatant of human synovial Fluid-derived mesenchymal stem cells inhibited senescence of stressed/Inflammatory licensed chondrocytes and delayed osteoarthritis progression.. Int. Immunopharmacol. 147, 113954.
    doi: 10.1016/j.intimp.2024.113954pubmed: 39756162google scholar: lookup
  97. Lin F, Zhang W, Xue D, Zhu T, Li J, Chen E. Signaling pathways involved in the effects of HMGB1 on mesenchymal stem cell migration and osteoblastic differentiation.. Int. J. Mol. Med. 37, 789–797.
    doi: 10.3892/ijmm.2016.2479pubmed: 26846297google scholar: lookup
  98. Linde P, Chow L, Sabino I, Williams Z, Impastato R, Dow S. Innate immune pathway activation to modulate mesenchymal stromal cell (MSC) interactions with synovium and cartilage.. Front. Bioeng. Biotechnol. 13, 1605148.
    doi: 10.3389/fbioe.2025.1605148pmc: PMC12370743pubmed: 40861855google scholar: lookup
  99. Liu H, Wu X, Gang N, Wang S, Deng W, Zan L. Macrophage functional phenotype can be consecutively and reversibly shifted to adapt to microenvironmental changes.. Int. J. Clin. Exp. Med. 15 (2), 3044–3053.
    pmc: PMC4402928pubmed: 25932281
  100. Liu Y, Zou R, Wang Z, Wen C, Zhang F, Lin F. Exosomal KLF3-AS1 from hMSCs promoted cartilage repair and chondrocyte proliferation in osteoarthritis.. Biochem. J. 475, 3629–3638.
    doi: 10.1042/BCJ20180675pubmed: 30341166google scholar: lookup
  101. Liu F, Qiu H, Xue M, Zhang S, Zhang X, Xu J. MSC-secreted TGF-β regulates lipopolysaccharide-stimulated macrophage M2-like polarization via the Akt/FoxO1 pathway.. Stem Cell Res. Ther. 10, 345.
    doi: 10.1186/s13287-019-1447-ypmc: PMC6878630pubmed: 31771622google scholar: lookup
  102. Liu W, Yu M, Xie D, Wang L, Ye C, Zhu Q. Melatonin-stimulated MSC-derived exosomes improve diabetic wound healing through regulating macrophage M1 and M2 polarization by targeting the PTEN/AKT pathway.. Stem Cell Res. Ther. 11, 259.
    doi: 10.1186/s13287-020-01756-xpmc: PMC7322868pubmed: 32600435google scholar: lookup
  103. Lozito T P, Tuan R S. Mesenchymal stem cells inhibit both endogenous and exogenous MMPs via secreted TIMPs.. J. Cell. Physiol. 226, 385–396.
    doi: 10.1002/jcp.22344pubmed: 20665704google scholar: lookup
  104. Luo D, Zhu H, Li S, Wang Z, Xiao J. Mesenchymal stem cell-derived exosomes as a promising cell-free therapy for knee osteoarthritis.. Front. Bioeng. Biotechnol. 12, 1309946.
    doi: 10.3389/fbioe.2024.1309946pmc: PMC10824863pubmed: 38292826google scholar: lookup
  105. Luo H, Lai Y, Tang W, Wang G, Shen J, Liu H. Mitochondrial transplantation: a promising strategy for treating degenerative joint diseases.. J. Transl. Med. 22, 941.
    doi: 10.1186/s12967-024-05752-0pmc: PMC11475785pubmed: 39407249google scholar: lookup
  106. Lüttichau I., Notohamiprodjo M., Wechselberger A., Peters C., Henger A., Seliger C., et al. (2005). Human adult CD34-progenitor cells functionally express the chemokine receptors CCR1, CCR4, CCR7, CXCR5, and CCR10 but not CXCR4. Stem Cells Dev. 14, 329–336. 10.1089/scd.2005.14.329
    doi: 10.1089/scd.2005.14.329pubmed: 15969628google scholar: lookup
  107. Mahrouf-Yorgov M., Augeul L., Da Silva C. C., Jourdan M., Rigolet M., Manin S., et al. (2017). Mesenchymal stem cells sense mitochondria released from damaged cells as danger signals to activate their rescue properties. CDD 24, 1224–1238. 10.1038/cdd.2017.51
    doi: 10.1038/cdd.2017.51pmc: PMC5520168pubmed: 28524859google scholar: lookup
  108. Malaise O., Paulissen G., Deroyer C., Ciregia F., Poulet C., Neuville S., et al. (2021). Influence of glucocorticoids on cellular senescence hallmarks in osteoarthritic fibroblast-like synoviocytes. J. Clin. Med. 10, 5331. 10.3390/jcm10225331
    doi: 10.3390/jcm10225331pmc: PMC8617749pubmed: 34830613google scholar: lookup
  109. Manferdini C., Maumus M., Gabusi E., Piacentini A., Filardo G., Peyrafitte J.-A., et al. (2013). Adipose-derived mesenchymal stem cells exert antiinflammatory effects on chondrocytes and synoviocytes from osteoarthritis patients through prostaglandin E2. Arthritis Rheum. 65, 1271–1281. 10.1002/art.37908
    doi: 10.1002/art.37908pubmed: 23613363google scholar: lookup
  110. Maumus M., Manferdini C., Toupet K., Peyrafitte J. A., Ferreira R., Facchini A., et al. (2013). Adipose mesenchymal stem cells protect chondrocytes from degeneration associated with osteoarthritis. Stem Cell Res. 11 (2), 834–844. 10.1016/j.scr.2013.05.008
    doi: 10.1016/j.scr.2013.05.008pubmed: 23811540google scholar: lookup
  111. Mayan M. D., Carpintero-Fernandez P., Gago-Fuentes R., Martinez-de-Ilarduya O., Wang H.-Z., Valiunas V., et al. (2013). Human articular chondrocytes express multiple gap junction proteins: differential expression of connexins in normal and osteoarthritic cartilage. Am. J. Pathol. 182, 1337–1346. 10.1016/j.ajpath.2012.12.018
    doi: 10.1016/j.ajpath.2012.12.018pmc: PMC3620397pubmed: 23416160google scholar: lookup
  112. Mehana E.-S. E., Khafaga A. F., El-Blehi S. S. (2019). The role of matrix metalloproteinases in osteoarthritis pathogenesis: an updated review. Life Sci. 234, 116786. 10.1016/j.lfs.2019.116786
    doi: 10.1016/j.lfs.2019.116786pubmed: 31445934google scholar: lookup
  113. Menarim B. C., Gillis K. H., Oliver A., Ngo Y., Werre S. R., Barrett S. H., et al. (2020). Macrophage activation in the synovium of healthy and osteoarthritic equine joints. Front. Vet. Sci. 7, 568756. 10.3389/fvets.2020.568756
    doi: 10.3389/fvets.2020.568756pmc: PMC7726135pubmed: 33324696google scholar: lookup
  114. Mia S., Warnecke A., Zhang X.-M., Malmström V., Harris R. A. (2014). An optimized protocol for human M2 macrophages using M-CSF and IL-4/IL-10/TGF-β yields a dominant immunosuppressive phenotype. Scand. J. Immunol. 79, 305–314. 10.1111/sji.12162
    doi: 10.1111/sji.12162pmc: PMC4282403pubmed: 24521472google scholar: lookup
  115. Mizenko R. R., Feaver M., Bozkurt B. T., Lowe N., Nguyen B., Huang K.-W., et al. (2024). A critical systematic review of extracellular vesicle clinical trials. JEV 13, e12510. 10.1002/jev2.12510
    doi: 10.1002/jev2.12510pmc: PMC11428870pubmed: 39330928google scholar: lookup
  116. Mosser D. M., Hamidzadeh K., Goncalves R. (2021). Macrophages and the maintenance of homeostasis. Cell Mol. Immunol. 18, 579–587. 10.1038/s41423-020-00541-3
    doi: 10.1038/s41423-020-00541-3pmc: PMC7491045pubmed: 32934339google scholar: lookup
  117. Müller-Ladner U., Ospelt C., Gay S., Distler O., Pap T. (2007). Cells of the synovium in rheumatoid arthritis. Synovial Fibroblasts. Arthritis Res. Ther. 9 (6), 223. 10.1186/ar2337
    doi: 10.1186/ar2337pmc: PMC2246247pubmed: 18177509google scholar: lookup
  118. Murphy J. M., Fink D. J., Hunziker E. B., Barry F. P. (2003). Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum. 48, 3464–3474. 10.1002/art.11365
    doi: 10.1002/art.11365pubmed: 14673997google scholar: lookup
  119. Murray P. J. (2017). Macrophage polarization. Annu. Rev. Physiol. 79, 541–566. 10.1146/annurev-physiol-022516-034339
    doi: 10.1146/annurev-physiol-022516-034339pubmed: 27813830google scholar: lookup
  120. Nakao Y., Fukuda T., Zhang Q., Sanui T., Shinjo T., Kou X., et al. (2021). Exosomes from TNF-α-treated human gingiva-derived MSCs enhance M2 macrophage polarization and inhibit periodontal bone loss. Acta Biomater. 122, 306–324. 10.1016/j.actbio.2020.12.046
    doi: 10.1016/j.actbio.2020.12.046pmc: PMC7897289pubmed: 33359765google scholar: lookup
  121. nNeybecker P., Henrionnet C., Pape E., Mainard D., Galois L., Loeuille D., et al. (2018). n and potentialities for cartilage repair from human advanced knee osteoarthritis synovial fluid-derived mesenchymal stem cells. Stem Cell Res. Ther.n9, 329. 10.1186/s13287-018-1071-2nn
    doi: 10.1186/s13287-018-1071-2pmc: PMC6263063pubmed: 30486903google scholar: lookup
  122. Nicolay N. H., Lopez Perez R., Debus J., Huber P. E. (2015). Mesenchymal stem cells – a new hope for radiotherapy-induced tissue damage? Cancer Lett. 366, 133–140. 10.1016/j.canlet.2015.06.012
    doi: 10.1016/j.canlet.2015.06.012pubmed: 26166559google scholar: lookup
  123. Oh J., Son Y. S., Kim W. H., Kwon O.-K., Kang B.-J. (2021). Mesenchymal stem cells genetically engineered to express platelet-derived growth factor and heme oxygenase-1 ameliorate osteoarthritis in a canine model. J. Orthop. Surg. Res. 16, 43. 10.1186/s13018-020-02178-4
    doi: 10.1186/s13018-020-02178-4pmc: PMC7802278pubmed: 33430899google scholar: lookup
  124. Park J.-Y., Kwon S., Kim S.-H., Kang Y. J., Khang D. (2020). Triamcinolone-gold nanoparticles repolarize synoviocytes and macrophages in an inflamed synovium. ACS Appl. Mater. Interfaces 12, 38936–38949. 10.1021/acsami.0c09842
    doi: 10.1021/acsami.0c09842pubmed: 32805872google scholar: lookup
  125. Phinney D. G., Di Giuseppe M., Njah J., Sala E., Shiva S., St Croix C. M., et al. (2015). Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs. Nat. Commun. 6, 8472. 10.1038/ncomms9472
    doi: 10.1038/ncomms9472pmc: PMC4598952pubmed: 26442449google scholar: lookup
  126. Pittenger M. F., Discher D. E., Péault B. M., Phinney D. G., Hare J. M., Caplan A. I. (2019). Mesenchymal stem cell perspective: cell biology to clinical progress. NPJ Regen. Med. 4, 22. 10.1038/s41536-019-0083-6
    doi: 10.1038/s41536-019-0083-6pmc: PMC6889290pubmed: 31815001google scholar: lookup
  127. Plattner B. L., Hostetter J. M. (2011). Comparative gamma delta T cell immunology: a focus on mycobacterial disease in cattle. Vet. Med. Int. 2011, 214384. 10.4061/2011/214384
    doi: 10.4061/2011/214384pmc: PMC3103839pubmed: 21647391google scholar: lookup
  128. Qi Z., Zhu J., Cai W., Lou C., Li Z. (2024). The role and intervention of mitochondrial metabolism in osteoarthritis. Mol. Cellular Biochemistry 479, 1513–1524. 10.1007/s11010-023-04818-9
    doi: 10.1007/s11010-023-04818-9pmc: PMC11224101pubmed: 37486450google scholar: lookup
  129. Rahmadian R., Adly M., Dilogo I. H., Revilla G., Ariliusra Z. (2024). Single intra-articular injection of human synovial membrane MSC from grade IV knee osteoarthritis patient improve cartilage repair in OA rat model. J. Orthop. Surg. Res. 19, 710. 10.1186/s13018-024-05149-1
    doi: 10.1186/s13018-024-05149-1pmc: PMC11531201pubmed: 39487527google scholar: lookup
  130. Rambold A. S., Lippincott-Schwartz J. (2011). Mechanisms of mitochondria and autophagy crosstalk. Cell Cycle 10, 4032–4038. 10.4161/cc.10.23.18384
    doi: 10.4161/cc.10.23.18384pmc: PMC3272286pubmed: 22101267google scholar: lookup
  131. Ren D., Zheng P., Zou S., Gong Y., Wang Y., Duan J., et al. (2022). GJA1-20K enhances mitochondria transfer from astrocytes to neurons via Cx43-TnTs after traumatic brain injury. Cell Mol. Neurobiol. 42, 1887–1895. 10.1007/s10571-021-01070-x
    doi: 10.1007/s10571-021-01070-xpmc: PMC11421752pubmed: 33728536google scholar: lookup
  132. Rendra E., Scaccia E., Bieback K. (2020). Recent advances in understanding mesenchymal stromal cells. F1000Res 27 (9), 156. 10.12688/f1000research.21862.1
    doi: 10.12688/f1000research.21862.1pmc: PMC7047922pubmed: 32148780google scholar: lookup
  133. Rieder B., Weihs A. M., Weidinger A., Szwarc D., Nürnberger S., Redl H., et al. (2018). Hydrostatic pressure-generated reactive oxygen species induce osteoarthritic conditions in cartilage pellet cultures. Sci. Rep. 8, 17010. 10.1038/s41598-018-34718-8
    doi: 10.1038/s41598-018-34718-8pmc: PMC6242959pubmed: 30451865google scholar: lookup
  134. Riegger J., Palm H. G., Brenner R. E. (2018). The functional role of chondrogenic stem/progenitor cells: novel evidence for immunomodulatory properties and regenerative potential after cartilage injury. eCM 36, 110–127. 10.22203/eCM.v036a09
    doi: 10.22203/eCM.v036a09pubmed: 30215457google scholar: lookup
  135. Rombouts W. J. C., Ploemacher R. E. (2003). Primary murine MSC show highly efficient homing to the bone marrow but lose homing ability following culture. Leukemia 17, 160–170. 10.1038/sj.leu.2402763
    doi: 10.1038/sj.leu.2402763pubmed: 12529674google scholar: lookup
  136. Roughley P. J., Lee E. R. (1994). Cartilage proteoglycans: structure and potential functions. Microsc. Res. Tech. 1 (5), 385–397. 10.1002/jemt.1070280505
    doi: 10.1002/jemt.1070280505pubmed: 7919526google scholar: lookup
  137. Rustom A., Saffrich R., Markovic I., Walther P., Gerdes H.-H. (2004). Nanotubular highways for intercellular organelle transport. Ann. N. Y. Acad. Sci. 303, 1007–1010. 10.1126/science.1093133
    doi: 10.1126/science.1093133pubmed: 14963329google scholar: lookup
  138. Sakaguchi Y., Sekiya I., Yagishita K., Muneta T. (2005). Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum. 52, 2521–2529. 10.1002/art.21212
    doi: 10.1002/art.21212pubmed: 16052568google scholar: lookup
  139. nScarfe L., Taylor A., Sharkey J., Harwood R., Barrow M., Comenge J., et al. (2018). Non-invasive imaging reveals conditions that impact distribution and persistence of cells after administration. Stem Cell Res. Ther.n9, 332. 10.1186/s13287-018-1076-xnn
    doi: 10.1186/s13287-018-1076-xpmc: PMC6264053pubmed: 30486897google scholar: lookup
  140. Scotece M., Vaamonde-García C., Lechuga-Vieco A. V., Cortés A. C., Gómez M. C. J., Filgueira-Fernández P., et al. (2022). mtDNA variability determines spontaneous joint aging damage in a conplastic mouse model. Aging (Albany NY). 2 14 (15), 5966–5983. 10.18632/aging.204153
    doi: 10.18632/aging.204153pmc: PMC9417242pubmed: 35779570google scholar: lookup
  141. Seol D., McCabe D. J., Choe H., Zheng H., Yu Y., Jang K., et al. (2012). Chondrogenic progenitor cells respond to cartilage injury. Arthritis Rheum. 64, 3626–3637. 10.1002/art.34613
    doi: 10.1002/art.34613pmc: PMC4950521pubmed: 22777600google scholar: lookup
  142. Singer N. G., Caplan A. I. (2011). Mesenchymal stem cells: mechanisms of inflammation. Annu. Rev. Pathol. 6, 457–478. 10.1146/annurev-pathol-011110-130230
    doi: 10.1146/annurev-pathol-011110-130230pubmed: 21073342google scholar: lookup
  143. Smith M. D. (2011). The normal synovium. Open Rheumatol. J. 5, 100–106. 10.2174/1874312901105010100
    doi: 10.2174/1874312901105010100pmc: PMC3263506pubmed: 22279508google scholar: lookup
  144. Smith R. K., Zunino L., Webbon P. M., Heinegård D. (1997). The distribution of cartilage oligomeric matrix protein (COMP) in tendon and its variation with tendon site, age and load. Matrix Biol. 16 (5), 255–271. 10.1016/s0945-053x(97)90014-7
    doi: 10.1016/s0945-053x(97)90014-7pubmed: 9501326google scholar: lookup
  145. Smyth J. W., Shaw R. M. (2013). Autoregulation of connexin43 gap junction formation by internally translated isoforms. Cell Rep. 5, 611–618. 10.1016/j.celrep.2013.10.009
    doi: 10.1016/j.celrep.2013.10.009pmc: PMC3898934pubmed: 24210816google scholar: lookup
  146. Song Y., Jorgensen C. (2022). Mesenchymal stromal cells in osteoarthritis: evidence for structural benefit and cartilage repair. Biomedicines 10, 1278. 10.3390/biomedicines10061278
    doi: 10.3390/biomedicines10061278pmc: PMC9219878pubmed: 35740299google scholar: lookup
  147. Spees J. L., Olson S. D., Whitney M. J., Prockop D. J. (2006). Mitochondrial transfer between cells can rescue aerobic respiration. Proc. Natl. Acad. Sci. U.S.A. 103 (5), 1283–1288. 10.1073/pnas.0510511103
    doi: 10.1073/pnas.0510511103pmc: PMC1345715pubmed: 16432190google scholar: lookup
  148. Sutherland T. E., Dyer D. P., Allen J. E. (2023). The extracellular matrix and the immune system: a mutually dependent relationship. Science 379, eabp8964. 10.1126/science.abp8964
    doi: 10.1126/science.abp8964pubmed: 36795835google scholar: lookup
  149. Tang S., Chen P., Zhang H., Weng H., Fang Z., Chen C., et al. (2021). Comparison of curative effect of human umbilical cord-derived mesenchymal stem cells and their small extracellular vesicles in treating osteoarthritis. Int. J. Nanomed. 16, 8185–8202. 10.2147/IJN.S336062
    doi: 10.2147/IJN.S336062pmc: PMC8687685pubmed: 34938076google scholar: lookup
  150. Thomas M. A., Fahey M. J., Pugliese B. R., Irwin R. M., Antonyak M. A., Delco M. L. (2022). Human mesenchymal stromal cells release functional mitochondria in extracellular vesicles. Front. Bioeng. Biotechnol. 10, 870193. 10.3389/fbioe.2022.870193
    doi: 10.3389/fbioe.2022.870193pmc: PMC9446449pubmed: 36082164google scholar: lookup
  151. Tonon R., D'Andrea P. (2000). Interleukin-1beta increases the functional expression of connexin 43 in articular chondrocytes: evidence for a Ca2+-dependent mechanism. JBMR 15, 1669–1677. 10.1359/jbmr.2000.15.9.1669
    doi: 10.1359/jbmr.2000.15.9.1669pubmed: 10976987google scholar: lookup
  152. Tu J., Hong W., Zhang P., Wang X., Körner H., Wei W. (2018). Ontology and function of fibroblast-like and macrophage-like synoviocytes: how do they talk to each other and can they be targeted for rheumatoid arthritis therapy? Front. Immunol. 9, 1467. 10.3389/fimmu.2018.01467
    doi: 10.3389/fimmu.2018.01467pmc: PMC6028561pubmed: 29997624google scholar: lookup
  153. Ullah M., Liu D. D., Thakor A. S. (2019). Mesenchymal stromal cell homing: mechanisms and strategies for improvement. iScience 15, 421–438. 10.1016/j.isci.2019.05.004
    doi: 10.1016/j.isci.2019.05.004pmc: PMC6529790pubmed: 31121468google scholar: lookup
  154. Vega-Letter A. M., García-Guerrero C., Yantén-Fuentes L., Pradenas C., Herrera-Luna Y., Lara-Barba E., et al. (2025). Safety and efficacy of mesenchymal stromal cells mitochondria transplantation as a cell-free therapy for osteoarthritis. J. Transl. Med. 23, 26. 10.1186/s12967-024-05945-7
    doi: 10.1186/s12967-024-05945-7pmc: PMC11706173pubmed: 39773289google scholar: lookup
  155. Velarde F., Ezquerra S., Delbruyere X., Caicedo A., Hidalgo Y., Khuory M. (2022). Mesenchymal stem cell-mediated transfer of mitochondria: mechanisms and functional impact. Cell. Mol. Life Sci. 79, 177. 10.1007/s00018-022-04207-3
    doi: 10.1007/s00018-022-04207-3pmc: PMC11073024pubmed: 35247083google scholar: lookup
  156. nViswanathan S., Shi Y., Galipeau J., Krampera M., Leblanc K., Martin I., et al. (2019). Mesenchymal stem stromal cells: International society for cell and gene therapy (ISCT®) mesenchymal stromal cell committee position statement on nomenclature. Cytotherapyn21, 1019–1024. 10.1016/j.jcyt.2019.08.002nn
    doi: 10.1016/j.jcyt.2019.08.002pubmed: 31526643google scholar: lookup
  157. nVorotnikova E., McIntosh D., Dewilde A., Zhang J., Reing J. E., Zhang L., et al. (2010). Extracellular matrix-derived products modulate endothelial and progenitor cell migration and proliferation and stimulate regenerative healing n. Matrix Biol.n29, 690–700. 10.1016/j.matbio.2010.08.007nn
    doi: 10.1016/j.matbio.2010.08.007pubmed: 20797438google scholar: lookup
  158. Wang K., Li Y., Zhu T., Zhang Y., Li W., Lin W., et al. (2017). Overexpression of c-Met in bone marrow mesenchymal stem cells improves their effectiveness in homing and repair of acute liver failure. Stem Cell Res. Ther. 8, 162. 10.1186/s13287-017-0614-2
    doi: 10.1186/s13287-017-0614-2pmc: PMC5499016pubmed: 28679425google scholar: lookup
  159. Wang R., Maimaitijuma T., Ma Y.-Y., Jiao Y., Cao Y.-P. (2020). Mitochondrial transfer from bone-marrow-derived mesenchymal stromal cells to chondrocytes protects against cartilage degenerative mitochondrial dysfunction in rats chondrocytes. Chin. Med. J. 134, 212–218. 10.1097/CM9.0000000000001057
    doi: 10.1097/CM9.0000000000001057pmc: PMC7817337pubmed: 32858593google scholar: lookup
  160. Wang S., Lei B., Zhang E., Gong P., Gu J., He L., et al. (2022). Targeted therapy for inflammatory diseases with mesenchymal stem cells and their derived exosomes: from basic to clinics. Int. J. Nanomed. 17, 1757–1781. 10.2147/IJN.S355366
    doi: 10.2147/IJN.S355366pmc: PMC9034888pubmed: 35469174google scholar: lookup
  161. Wang Y., Cheng H., Wang T., Zhang K., Zhang Y., Kang X. (2023). Oxidative stress in intervertebral disc degeneration: molecular mechanisms, pathogenesis and treatment. Cell Prolif. 56, e13448. 10.1111/cpr.13448
    doi: 10.1111/cpr.13448pmc: PMC10472537pubmed: 36915968google scholar: lookup
  162. Watt F. E., Paterson E., Freidin A., Kenny M., Judge A., Saklatvala J., et al. (2016). Acute molecular changes in synovial fluid following human knee injury: association with early clinical outcomes. Arthritis Rheumatol. 68, 2129–2140. 10.1002/art.39677
    doi: 10.1002/art.39677pmc: PMC5006850pubmed: 26991527google scholar: lookup
  163. Wei P., Bao R. (2022). Intra-articular mesenchymal stem cell injection for knee osteoarthritis: mechanisms and clinical evidence. Int. J. Mol. Sci. 24, 59. 10.3390/ijms24010059
    doi: 10.3390/ijms24010059pmc: PMC9819973pubmed: 36613502google scholar: lookup
  164. Wen C., Lin L., Zou R., Lin F., Liu Y. (2022). Mesenchymal stem cell-derived exosome mediated long non-coding RNA KLF3-AS1 represses autophagy and apoptosis of chondrocytes in osteoarthritis. Cell CycleGeorget. Tex. 21, 289–303. 10.1080/15384101.2021.2019411
    doi: 10.1080/15384101.2021.2019411pmc: PMC8855872pubmed: 34964696google scholar: lookup
  165. nWesdorp M. A., Bastiaansen-Jenniskens Y. M., Capar S., Verhaar J. A. N., Narcisi R., van Osch G. J. V. M. (2022). Modulation of inflamed synovium improves migration of mesenchymal stromal cells through anti-inflammatory macrophages. Cartilagen13, 19476035221085136. 10.1177/19476035221085136nn
    doi: 10.1177/19476035221085136pmc: PMC9137323pubmed: 35306879google scholar: lookup
  166. Wright K., McDonald J., Mennan C., Perry J., Peffers M., Hulme C. (2023). Synovial fluid proteomics and bioinformatics highlights potential mechanisms of umbilical Cord-MSC induced radiological improvement in an ovine model of osteoarthritis. Bone Jt. J. 105-B, 53. 10.1302/1358-992X.2023.16.053
    doi: 10.1302/1358-992X.2023.16.053google scholar: lookup
  167. Wynn R. F., Hart C. A., Corradi-Perini C., O'Neill L., Evans C. A., Wraith J. E., et al. (2004). A small proportion of mesenchymal stem cells strongly expresses functionally active CXCR4 receptor capable of promoting migration to bone marrow. Blood 104, 2643–2645. 10.1182/blood-2004-02-0526
    doi: 10.1182/blood-2004-02-0526pubmed: 15251986google scholar: lookup
  168. Xu B., Li J., Wu C., Liu C., Yan X., Chang X. (2018). CXCL10 and TRAIL are upregulated by TXNDC5 in rheumatoid arthritis fibroblast-like synoviocytes. J. Rheumatol. 45, 335–340. 10.3899/jrheum.170170
    doi: 10.3899/jrheum.170170pubmed: 29247155google scholar: lookup
  169. Yan L., Li D., Li S., Jiao Li J., Du G., Liu H., et al. (2024). Exosomes derived from 3D-cultured MSCs alleviate knee osteoarthritis by promoting M2 macrophage polarization through miR-365a-5p and inhibiting TLR2/Myd88/NF-κB pathway. Chem. Eng. J. 497, 154432. 10.1016/j.cej.2024.154432
    doi: 10.1016/j.cej.2024.154432google scholar: lookup
  170. Yang C.-Y., Chanalaris A., Troeberg L. (2017). ADAMTS and ADAM metalloproteinases in osteoarthritis - looking beyond the 'usual suspects. Osteoarthr. Cartil. 25, 1000–1009. 10.1016/j.joca.2017.02.791
    doi: 10.1016/j.joca.2017.02.791pmc: PMC5473942pubmed: 28216310google scholar: lookup
  171. nYang J., Xiao Y., Tang Z., Luo Z., Li D., Wang Q., et al. (2020). The negatively charged microenvironment of collagen hydrogels regulates the chondrogenic differentiation of bone marrow mesenchymal stem cells and n. J. Mater. Chem. Bn8, 4680–4693. 10.1039/d0tb00172dnn
    doi: 10.1039/d0tb00172dpubmed: 32391834google scholar: lookup
  172. Yang J., Liu L., Oda Y., Wada K., Ago M., Matsuda S., et al. (2023). Extracellular vesicles and Cx43-Gap junction channels are the main routes for mitochondrial transfer from ultra-purified mesenchymal stem cells, RECs. Int. J. Mol. Sci. 24, 10294. 10.3390/ijms241210294
    doi: 10.3390/ijms241210294pmc: PMC10299354pubmed: 37373439google scholar: lookup
  173. Yang H., Zhou Y., Ying B., Dong X., Qian Q., Gao S. (2024). Effects of human umbilical cord mesenchymal stem cell-derived exosomes in the rat osteoarthritis models. Stem Cell Transl. Med. 13, 803–811. 10.1093/stcltm/szae031
    doi: 10.1093/stcltm/szae031pmc: PMC11328936pubmed: 38913985google scholar: lookup
  174. Yao Y., Fan X.-L., Jiang D., Zhang Y., Li X., Xu Z.-B., et al. (2018). Connexin 43-Mediated mitochondrial transfer of iPSC-MSCs alleviates asthma inflammation. Stem Cell Rep. 11, 1120–1135. 10.1016/j.stemcr.2018.09.012
    doi: 10.1016/j.stemcr.2018.09.012pmc: PMC6234920pubmed: 30344008google scholar: lookup
  175. Yao Q., Wu X., Tao C., Gong W., Chen M., Qu M., et al. (2023). Osteoarthritis: pathogenic signaling pathways and therapeutic targets. Signal Transduct. Target. Ther. 8, 56. 10.1038/s41392-023-01330-w
    doi: 10.1038/s41392-023-01330-wpmc: PMC9898571pubmed: 36737426google scholar: lookup
  176. Yin Z., Dong C., Jiang K., Xu Z., Li R., Guo K., et al. (2019). Heterogeneity of cancer-associated fibroblasts and roles in the progression, prognosis, and therapy of hepatocellular carcinoma. J. Hematol. Oncol. 12, 101. 10.1186/s13045-019-0782-x
    doi: 10.1186/s13045-019-0782-xpmc: PMC6757399pubmed: 31547836google scholar: lookup
  177. Yu Y., Zheng H., Buckwalter J. A., Martin J. A. (2014). Single cell sorting identifies progenitor cell population from full thickness bovine articular cartilage. Osteoarthr. Cartil. 22, 1318–1326. 10.1016/j.joca.2014.07.002
    doi: 10.1016/j.joca.2014.07.002pmc: PMC4950515pubmed: 25038490google scholar: lookup
  178. Yukawa H., Watanabe M., Kaji N., Okamoto Y., Tokeshi M., Miyamoto Y., et al. (2012). Monitoring transplanted adipose tissue-derived stem cells combined with heparin in the liver by fluorescence imaging using quantum dots. Biomaterials 33, 2177–2186. 10.1016/j.biomaterials.2011.12.009
    doi: 10.1016/j.biomaterials.2011.12.009pubmed: 22192539google scholar: lookup
  179. Zare R., Tanideh N., Nikahval B., Mirtalebi M. S., Ahmadi N., Zarea S., et al. (2020). Are stem cells derived from synovium and fat pad able to treat induced knee osteoarthritis in rats? Int. J. Rheumatol. 2020, 9610261. 10.1155/2020/9610261
    doi: 10.1155/2020/9610261pmc: PMC7374223pubmed: 32765610google scholar: lookup
  180. Zeng G. Q., Chen A. B., Li W., Song J. H., Gao C. Y. (2015). High MMP-1, MMP-2, and MMP-9 protein levels in osteoarthritis. GMR 14, 14811–14822. 10.4238/2015.November.18.46
    doi: 10.4238/2015.November.18.46pubmed: 26600542google scholar: lookup
  181. Zhang Q., Chen Y., Wang Q., Fang C., Sun Y., Yuan T., et al. (2016). Effect of bone marrow-derived stem cells on chondrocytes from patients with osteoarthritis. Mol. Med. Rep. 13, 1795–1800. 10.3892/mmr.2015.4720
    doi: 10.3892/mmr.2015.4720pubmed: 26707906google scholar: lookup
  182. Zhang H., Lin C., Zeng C., Wang Z., Wang H., Lu J., et al. (2018). Synovial macrophage M1 polarisation exacerbates experimental osteoarthritis partially through R-spondin-2. Ann. Rheum. Dis. 77, 1524–1534. 10.1136/annrheumdis-2018-213450
    doi: 10.1136/annrheumdis-2018-213450pubmed: 29991473google scholar: lookup
  183. Zhang S., Hu B., Liu W., Wang P., Lv X., Chen S., et al. (2020). Articular cartilage regeneration: the role of endogenous mesenchymal stem/progenitor cell recruitment and migration. Semin. Arthritis Rheum. 50, 198–208. 10.1016/j.semarthrit.2019.11.001
    doi: 10.1016/j.semarthrit.2019.11.001pubmed: 31767195google scholar: lookup
  184. nZheng J., Li H., He L., Huang Y., Cai J., Chen L., et al. (2019). Preconditioning of umbilical cord-derived mesenchymal stem cells by rapamycin increases cell migration and ameliorates liver ischaemia/reperfusion injury in mice the CXCR4/CXCL12 axis. Cell Prolif.n52, e12546. 10.1111/cpr.12546nn
    doi: 10.1111/cpr.12546pmc: PMC6496237pubmed: 30537044google scholar: lookup
  185. Zhou S., Wen H., Cai W., Zhang Y., Li H. (2019). Effect of hypoxia/reoxygenation on the biological effect of IGF system and the inflammatory mediators in cultured synoviocytes. Biochem. Biophys. Res. Commun. 508, 17–24. 10.1016/j.bbrc.2018.11.099
    doi: 10.1016/j.bbrc.2018.11.099pubmed: 30466784google scholar: lookup
  186. Zhou H., Shen X., Yan C., Xiong W., Ma Z., Tan Z., et al. (2022). Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate osteoarthritis of the knee in mice model by interacting with METTL3 to reduce m6A of NLRP3 in macrophage. Stem Cell Res. Ther. 13, 322. 10.1186/s13287-022-03005-9
    doi: 10.1186/s13287-022-03005-9pmc: PMC9288728pubmed: 35842714google scholar: lookup
  187. Zhu J., Zhou J., Feng B., Pan Q., Yang J., Lang G., et al. (2024). MSCs alleviate LPS-induced acute lung injury by inhibiting the proinflammatory function of macrophages in mouse lung organoid-macrophage model. Cell. Mol. Life Sci. 81, 124. 10.1007/s00018-024-05150-1
    doi: 10.1007/s00018-024-05150-1pmc: PMC10927843pubmed: 38466420google scholar: lookup
  188. Zong Y., Li H., Liao P., Chen L., Pan Y., Zheng Y., et al. (2024). Mitochondrial dysfunction: mechanisms and advances in therapy. Signal Transduct. Target. Ther. 9, 124. 10.1038/s41392-024-01839-8
    doi: 10.1038/s41392-024-01839-8pmc: PMC11094169pubmed: 38744846google scholar: lookup

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