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BibTex RIS Kaynak Göster

A review of exosomes derived from mesenchymal stem cells as a treatment approach for temporomandibular disorders

Yıl 2026, Cilt: 65 Sayı: 1, 194 - 205, 09.03.2026

Fulya Gürcan , Deniz Özen , Gözde Işık , Yiğit Uyanıkgil

https://doi.org/10.19161/etd.1759166
https://izlik.org/JA29UD62UT

Öz

Stem cell-based therapies are contemporary approaches that particularly involve the use of mesenchymal stem cells. Mesenchymal stem cells are multipotent precursors capable of differentiating from various cell sources, including adipocytes, myocytes, osteoblasts, and chondrocytes. They have self-renewal capabilities and possess properties that support hemostasis, reduce inflammation, modulate the immune response, and promote tissue regeneration. The paracrine activity of mesenchymal stem cells serves as a significant mechanism for their therapeutic efficacy. Recently, there has been a growing interest in the secretomes of mesenchymal stem cells which consist of growth factors, cytokines, chemokines, and extracellular vesicles. Extracellular vesicles are classified into two subtypes: ectosomes and exosomes. These secretions hold potential as innovative tools in regenerative medicine and dentistry for diagnosing, managing, and monitoring various diseases. This review focused on mesenchymal stem cells-derived exosomes and their potential as an alternative strategy for the therapeutic management of temporomandibular disorders. It also summarized the benefits and drawbacks associated with this treatment

Anahtar Kelimeler

Stem cell exosome temporomandibular joint regeneration inflammation

Etik Beyan

This is a review article that does not require ethical approval

Destekleyen Kurum

-

Proje Numarası

-

Teşekkür

-

Kaynakça

  • 1. Wang XD, Zhang JN, Gan YH, Zhou YH. Current understanding of pathogenesis and treatment of TMJ osteoarthritis. J Dent Res. 2015;94(5):666-73. https://doi.org/10.1177/0022034515574770
  • Almeida LE, Doetzer A, Beck ML. Immunohistochemical Markers of Temporomandibular Disorders: A Review of the Literature. J Clin Med. 2023;18:12(3):789. https://doi: 10.3390/jcm12030789.
  • Hill CN, Coombs MC, Cisewski SE, Durham EL, Bonthius DJ, Gardner GM, et al. Structure-function relationships of TMJ lateral capsule-ligament complex. J Biomech. 2022;130:110889. . https://doi.org/10.1016/j.jbiomech.2021.110889
  • Nickel, J. C., Iwasaki, L. R., Gonzalez, Y. M., Gallo, L. M., & Yao, H. Mechanobehavior and Ontogenesis of the Temporomandibular Joint. Journal of dental research. 2018;97(11):1185–92. https://doi.org/10.1177/0022034518786469
  • Schiffman, E., Ohrbach, R., Truelove, E., Look, J., Anderson, G., Goulet, J. P., et al. Orofacial Pain Special Interest Group, International Association for the Study of Pain. Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for Clinical and Research Applications: recommendations of the International RDC/TMD Consortium Network* and Orofacial Pain Special Interest Group†. Journal of oral & facial pain and headache, 2014;28(1):6–27. https://doi.org/10.11607/jop.1151
  • González-Sánchez B, García Monterey P, Ramírez-Durán MDV, Garrido-Ardila EM, Rodríguez-Mansilla J, Jiménez-Palomares M. Temporomandibular Joint Dysfunctions: A Systematic Review of Treatment Approaches. J Clin Med. 2023;12(12):4156. https://doi.org/10.3390/jcm12124156.
  • Al-Moraissi EA, Farea R, Qasem KA, Al-Wadeai MS, Al-Sabahi ME, Al-Iryani GM. Effectiveness of occlusal splint therapy in the management of temporomandibular disorders: network meta-analysis of randomized controlled trials. Int J Oral Maxillofac Surg. 2020;49(8):1042-56. . https://doi.org/10.1016/j.ijom.2020.01.004.
  • Asquini G, Pitance L, Michelotti A, Falla D. Effectiveness of manual therapy applied to craniomandibular structures in temporomandibular disorders: A systematic review. J Oral Rehabil. 2022;49(4):442-55. . https://doi.org/10.1111/joor.13299.
  • Xu J, Ren H, Zhao S, Li Q, Li C, Bao G, et al. Comparative effectiveness of hyaluronic acid, platelet-rich plasma, and platelet-rich fibrin in treating temporomandibular disorders: a systematic review and network meta-analysis. Head Face Med. 2023;19(1):39. https://doi.org/10.1186/s13005-023-00369.
  • Hu Y, Zhang X, Liu S, Xu F. Ultrasound-guided vs conventional arthrocentesis for management of temporomandibular joint disorders: A systematic review and meta-analysis. Cranio. 2023;41(3):264-73. . https://doi.org/10.1080/08869634.2020.1829870.
  • Peres Lima FGG, Rios LGC, Bianchi J, Gonçalves JR, Paranhos LR, Vieira WA, et al.Complications of total temporomandibular joint replacement: a systematic review and meta-analysis. Int J Oral Maxillofac Surg. 2023;52(5):584-94. https://doi.org/10.1016/j.ijom.2022.10.009
  • Badawy AA, El-Hofey SM, Shaban AM, Orif SE, Uyanıkgil Y, El-Magd MA. Camel milk extracellular vesicles/exosomes: a fascinating frontier in isolation and therapeutic potential. Food Funct. 2025;20;16(2):344-365. https://doi.org/10.1039/d4fo04331f.
  • Pan B.T., Teng K., Wu C., Adam M., Johnstone R.M.x. Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J. Cell Biol. 1985;101(3):942–48. https://doi.org/10.1083/jcb.101.3.942 Volume 65 Issue 1, March 2026 / Cilt 65 Sayı 1, Mart 2026 203
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Temporomandibular eklem bozukluklarında tedavi yaklaşımı olarak kullanılan mezenkimal kök hücre kaynaklı eksozomlar üzerine bir derleme

Yıl 2026, Cilt: 65 Sayı: 1, 194 - 205, 09.03.2026

Fulya Gürcan , Deniz Özen , Gözde Işık , Yiğit Uyanıkgil

https://doi.org/10.19161/etd.1759166
https://izlik.org/JA29UD62UT

Öz

Kök hücre temelli uygulamalar, mezenkimal kök hücrelerin yaygın olarak kullanıldığı güncel tedavi yaklaşımlarıdır. Mezenkimal kök hücreler, yağ hücreleri, miyosit, osteoblast ve kondrositler dâhil olmak üzere çeşitli hücre kaynaklarından farklılaşabilen çok potansiyelli öncülerdir. Kendi kendilerini yenileyebilirler ve hemostaz, inflamasyon süreçleri, bağışıklık mekanizması, doku tamiri gibi birçok hücresel yanıtta rol oynarlar. Mezenkimal kök hücrelerin parakrin etkisi, terapötik etkinlikleri için önemli bir mekanizma görevi görür. Son dönemde, büyüme faktörleri, sitokinler, kemokinler ve hücre dışı veziküller gibi mezenkimal kök hücre kaynaklı sekretomlara artan bir ilgi mevcuttur. Bu sekretomlardan olan hücre dışı veziküller iki alt tipe ayrılır: ektozomlar ve ekzosomlar. Eksozomlar, rejeneratif tıp ve diş hekimliğinde çeşitli hastalıkların teşhisi, yönetimi ve takibi için yenilikçi araçlar olarak potansiyel taşımaktadır. Bu derlemede, mezenkimal kök hücre kökenli eksozomlar ve eksozomların, temporomandibular eklem bozukluklarının terapötik tedavisinde alternatif bir uygulama olarak potansiyelleri incelenmiştir. Ayrıca, bu tedavinin sunduğu faydalar ve olası dezavantajları da özetlenmiştir.

Anahtar Kelimeler

Kök hücre eksozom temporomandibular eklem yenilenme inflamasyon

Proje Numarası

-

Kaynakça

  • 1. Wang XD, Zhang JN, Gan YH, Zhou YH. Current understanding of pathogenesis and treatment of TMJ osteoarthritis. J Dent Res. 2015;94(5):666-73. https://doi.org/10.1177/0022034515574770
  • Almeida LE, Doetzer A, Beck ML. Immunohistochemical Markers of Temporomandibular Disorders: A Review of the Literature. J Clin Med. 2023;18:12(3):789. https://doi: 10.3390/jcm12030789.
  • Hill CN, Coombs MC, Cisewski SE, Durham EL, Bonthius DJ, Gardner GM, et al. Structure-function relationships of TMJ lateral capsule-ligament complex. J Biomech. 2022;130:110889. . https://doi.org/10.1016/j.jbiomech.2021.110889
  • Nickel, J. C., Iwasaki, L. R., Gonzalez, Y. M., Gallo, L. M., & Yao, H. Mechanobehavior and Ontogenesis of the Temporomandibular Joint. Journal of dental research. 2018;97(11):1185–92. https://doi.org/10.1177/0022034518786469
  • Schiffman, E., Ohrbach, R., Truelove, E., Look, J., Anderson, G., Goulet, J. P., et al. Orofacial Pain Special Interest Group, International Association for the Study of Pain. Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for Clinical and Research Applications: recommendations of the International RDC/TMD Consortium Network* and Orofacial Pain Special Interest Group†. Journal of oral & facial pain and headache, 2014;28(1):6–27. https://doi.org/10.11607/jop.1151
  • González-Sánchez B, García Monterey P, Ramírez-Durán MDV, Garrido-Ardila EM, Rodríguez-Mansilla J, Jiménez-Palomares M. Temporomandibular Joint Dysfunctions: A Systematic Review of Treatment Approaches. J Clin Med. 2023;12(12):4156. https://doi.org/10.3390/jcm12124156.
  • Al-Moraissi EA, Farea R, Qasem KA, Al-Wadeai MS, Al-Sabahi ME, Al-Iryani GM. Effectiveness of occlusal splint therapy in the management of temporomandibular disorders: network meta-analysis of randomized controlled trials. Int J Oral Maxillofac Surg. 2020;49(8):1042-56. . https://doi.org/10.1016/j.ijom.2020.01.004.
  • Asquini G, Pitance L, Michelotti A, Falla D. Effectiveness of manual therapy applied to craniomandibular structures in temporomandibular disorders: A systematic review. J Oral Rehabil. 2022;49(4):442-55. . https://doi.org/10.1111/joor.13299.
  • Xu J, Ren H, Zhao S, Li Q, Li C, Bao G, et al. Comparative effectiveness of hyaluronic acid, platelet-rich plasma, and platelet-rich fibrin in treating temporomandibular disorders: a systematic review and network meta-analysis. Head Face Med. 2023;19(1):39. https://doi.org/10.1186/s13005-023-00369.
  • Hu Y, Zhang X, Liu S, Xu F. Ultrasound-guided vs conventional arthrocentesis for management of temporomandibular joint disorders: A systematic review and meta-analysis. Cranio. 2023;41(3):264-73. . https://doi.org/10.1080/08869634.2020.1829870.
  • Peres Lima FGG, Rios LGC, Bianchi J, Gonçalves JR, Paranhos LR, Vieira WA, et al.Complications of total temporomandibular joint replacement: a systematic review and meta-analysis. Int J Oral Maxillofac Surg. 2023;52(5):584-94. https://doi.org/10.1016/j.ijom.2022.10.009
  • Badawy AA, El-Hofey SM, Shaban AM, Orif SE, Uyanıkgil Y, El-Magd MA. Camel milk extracellular vesicles/exosomes: a fascinating frontier in isolation and therapeutic potential. Food Funct. 2025;20;16(2):344-365. https://doi.org/10.1039/d4fo04331f.
  • Pan B.T., Teng K., Wu C., Adam M., Johnstone R.M.x. Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J. Cell Biol. 1985;101(3):942–48. https://doi.org/10.1083/jcb.101.3.942 Volume 65 Issue 1, March 2026 / Cilt 65 Sayı 1, Mart 2026 203
  • Harding C., Heuser J., Stahl P. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J. Cell Biol. 1983;97:329–39 https://doi.org/10.1083/jcb.97.2.329
  • Tan F, Li X, Wang Z, Li J, Shahzad K, Zheng J. Clinical applications of stem cell-derived exosomes. Signal Transduct Target Ther. 2024;9(1):17. https://doi.org/10.1038/s41392-023-01704-0.
  • Lotfy A, AboQuella NM, Wang H. Mesenchymal stromal/stem cell (MSC)-derived exosomes in clinical trials. Stem Cell Res Ther. 2023;14(1):66. https://doi.org/10.1186/s13287-023-03287-7.
  • Hade MD, Suire CN, Suo Z. Mesenchymal Stem Cell-Derived Exosomes: Applications in Regenerative Medicine. Cells. 2021;10(8):1959. https://doi.org/10.3390/cells10081959.
  • Ma CY, Zhai Y, Li CT, Liu J, Xu X, Chen H, et al. Translating mesenchymal stem cell and their exosome research into GMP compliant advanced therapy products: Promises, problems and prospects. Med Res Rev. 2024;44(3):919-38. https://doi.org/10.1002/med.22002.
  • Ren K. Exosomes in perspective: a potential surrogate for stem cell therapy. Odontology. 2019;107:271–84. https://doi.org/10.1007/s10266-018-0395-9.
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  • Altıntaş Ö, Saylan Y. Exploring the Versatility of Exosomes: A Review on Isolation, Characterization, Detection Methods, and Diverse Applications. Anal Chem. 2023;95(44):16029-48. https://doi.org/10.1021/acs.analchem.3c02224.
  • Yousif G, Qadri S, Parray A, Akhthar N, Shuaib A, Haik Y. Exosomes Derived Neuronal Markers: Immunoaffinity Isolation and Characterization. Neuromolecular Med. 2022;24(3):339-51. https://doi.org/10.1007/s12017-021-08696-6.
  • Sidhom K, Obi PO, Saleem A. A Review of Exosomal Isolation Methods: Is Size Exclusion Chromatography the Best Option? Int J Mol Sci. 2020;21(18):6466. https://doi.org/10.3390/ijms21186466.
  • Zhao L, Wang H, Fu J, Wu X, Liang XY, Liu XY, et al. Microfluidic-based exosome isolation and highly sensitive aptamer exosome membrane protein detection for lung cancer diagnosis. Biosens Bioelectron. 2022;214:114487. https://doi.org/10.1016/j.bios.2022.114487. 204 Ege Journal of Medicine / Ege Tıp Dergisi
  • Skuratovskaia D, Vulf M, Khaziakhmatova O, Malashchenko V, Komar A, Shunkin E, et al. Exosome Limitations in the Treatment of Inflammatory Diseases. Curr Pharm Des. 2021;27(28):3105-21. https://doi.org/10.2174/1381612826666201210120444.
  • Wu Y, Wang Y, Lu Y, Luo X, Huang Y, Xie T, et al. Microfluidic Technology for the Isolation and Analysis of Exosomes. Micromachines (Basel). 2022;13(10):1571. https://doi.org/10.3390/mi13101571.
  • Padinharayil H, Varghese J, Wilson C, George A. Mesenchymal stem cell-derived exosomes: Characteristics and applications in disease pathology and management. Life Sci. 2024;342:122542. https://doi.org/10.1016/j.lfs.2024.122542.
  • Chu WC, Zhang S, Sng TJ, Ong YJ, Tan WL, Ang VY, et al. Distribution of pericellular matrix molecules in the temporomandibular joint and their chondroprotective effects against inflammation. Int J Oral Sci. 2017;9(1):43-52. https://doi.org/10.1038/ijos.2016.57.
  • Qiao Y, Li J, Yuh C, Ko F, Mercuri LG, Alkhudari J,et al. Chemokine Regulation in Temporomandibular Joint Disease: A Comprehensive Review. Genes (Basel). 2023;14(2):408. https://doi.org/10.3390/genes14020408.
  • Wang Y, Zhao M, Li W, Yang Y, Zhang Z, Ma R, et al. BMSC-Derived Small Extracellular Vesicles Induce Cartilage Reconstruction of Temporomandibular Joint Osteoarthritis via Autotaxin-YAP Signaling Axis. Front Cell Dev Biol. 2021;9:656153. https://doi.org/10.3389/fcell.2021.656153.
  • Ferreira LM, Moura ÁF, Barbosa GA, Pereira HS, Dos Santos Calderon P. Do matrix metalloproteinases play a role in degenerative disease of temporomandibular joint? A systematic review. Cranio. 2016;34(2):112-7. https://doi.org/10.1179/2151090314Y.0000000034.
  • Nascimento GC, De Paula BB, Gerlach RF, Leite-Panissi CRA. Temporomandibular inflammation regulates the matrix metalloproteinases MMP-2 and MMP-9 in limbic structures. J Cell Physiol. 2021;236(9):6571-80. https://doi.org/10.1002/jcp.30341.
  • Asgarpour K, Shojaei Z, Amiri F, Ai J, Mahjoubin-Tehran M, Ghasemi F, et al. Exosomal microRNAs derived from mesenchymal stem cells: cell-to-cell messages. Cell Commun Signal. 2020;18(1):149. https://doi.org/10.1186/s12964-020-00650-6.
  • Luo P, Jiang C, Ji P, Wang M, Xu J. Exosomes of stem cells from human exfoliated deciduous teeth as an anti-inflammatory agent in temporomandibular joint chondrocytes via miR-100-5p/mTOR. Stem Cell Res Ther. 2019;10(1):216. https://doi.org/10.1186/s13287-019-1341-7.
  • Chamberlain CS, Prabahar A, Kink JA, Mueller E, Li Y, Yopp S, et al.Modulating the mesenchymal stromal cell microenvironment alters exosome RNA content and ligament healing capacity. Stem Cells. 2024;42(7):636-49. https://doi.org/10.1093/stmcls/sxae028.
  • Lei Z, Chen X, Chen K, Liu P, Ao M, Gan L, et al. Exosome-like vesicles encapsulated with specific microRNAs accelerate burn wound healing and ameliorate scarring. J Nanobiotechnology. 2025;23(1):264. https://doi.org/10.1186/s12951-025-03337-7.
  • Yang X, Zhang S, Lu J, Chen X, Zheng T, He R, et al. Therapeutic potential of mesenchymal stem cell-derived exosomes in skeletal diseases. Front Mol Biosci. 2024;11:1268019. https://doi.org/10.3389/fmolb.2024.1268019.
  • Xu Y, Wei C, Ma L, Zhao L, Li D, Lin Y, et al. 3D mesenchymal stem cell exosome-functionalized hydrogels for corneal wound healing. J Control Release. 2025;380:630-46. https://doi.org/10.1016/j.jconrel.2025.02.030.
  • Liu Y, Zhang Z, Wang B, Dong Y, Zhao C, Zhao Y, et al. Inflammation-Stimulated MSC-Derived Small Extracellular Vesicle miR-27b-3p Regulates Macrophages by Targeting CSF-1 to Promote Temporomandibular Joint Condylar Regeneration. Small. 2022;18(16):e2107354. https://doi.org/10.1002/smll.202107354.
  • Qiu B, Xu X, Yi P, Hao Y. Curcumin reinforces MSC-derived exosomes in attenuating osteoarthritis via modulating the miR-124/NF-kB and miR-143/ROCK1/TLR9 signalling pathways. J Cell Mol Med. 2020;24(18):10855-65. https://doi.org/10.1111/jcmm.15714.
  • Yuan W, Liu J, Zhang Z, Ye C, Zhou X, Yi Y, et al. Strontium-Alix interaction enhances exosomal miRNA selectively loading in synovial MSCs for temporomandibular joint osteoarthritis treatment. Int J Oral Sci. 2025;17(1):6. https://doi.org/10.1038/s41368-024-00329-5. Volume 65 Issue 1, March 2026 / Cilt 65 Sayı 1, Mart 2026 205
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  • Nahm, W.J., Thunga, S. and Yoo, J.Complications After Exosome Treatment for Aesthetic Skin Rejuvenation. Dermatological Reviews, 2024;5: e242. https://doi.org/10.1002/der2.242
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  • Choi H, Kwak JH, Shin BS, Na CH, Kim MS. Foreign body granuloma caused by an injection of exosomes. JAAD, 2024
  • Kolhe R, Hunter M, Liu S, Jadeja RN, Pundkar C, Mondal AK, et al. Gender-specific differential expression of exosomal miRNA in synovial fluid of patients with osteoarthritis. Sci Rep 2017;7(1): 2029. http://dx.doi.org/10.1038/s41598-017-01905-y
  • Song JE, Shin JH, Moon KW, et al. AB0070 A role of rynovial exosomes in Osteoclast differentiation of inflammatory arthritis. Ann Rheum Dis 2016;75: 921-1.
  • Chen J, Tan Y, Chen Z, Yang H, Li X, Long X, et al. Exosomes derived from primary cartilage stem/progenitor cells promote the repair of osteoarthritic chondrocytes by modulating immune responses. Int. Immunopharmacol. 2024; 2024;143(Pt2):113397. http://dx.doi.org/10.1016/j.intimp.2024.113397
  • Wang Z, Hu Z, Niu L, Xu Y, Qi Y. Mesenchymal stem cell-derived exosomes for the treatment of knee osteoarthritis: a systematic review and meta-analysis based on rat model. Front Pharmacol. 2025;16:1588841. http://dx.doi.org/10.3389/fphar.2025.1588841.
Toplam 65 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Ağız, Yüz ve Çene Cerrahisi, Rejeneratif Tıp (kök hücreler dahil)
Bölüm Derleme
Yazarlar

Fulya Gürcan 0009-0000-6787-1685

Deniz Özen 0009-0009-7192-9208

Gözde Işık 0000-0001-9572-3049

Yiğit Uyanıkgil 0000-0002-4016-0522

Proje Numarası -
Gönderilme Tarihi 7 Ağustos 2025
Kabul Tarihi 18 Kasım 2025
Yayımlanma Tarihi 9 Mart 2026
DOI https://doi.org/10.19161/etd.1759166
IZ https://izlik.org/JA29UD62UT
Yayımlandığı Sayı Yıl 2026 Cilt: 65 Sayı: 1

Kaynak Göster

Vancouver 1.Fulya Gürcan, Deniz Özen, Gözde Işık, Yiğit Uyanıkgil. A review of exosomes derived from mesenchymal stem cells as a treatment approach for temporomandibular disorders. ETD. 01 Mart 2026;65(1):194-205. doi:10.19161/etd.1759166

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