Stem Cell Therapy in Maxillofacial Surgery: A Literature Review

Öz

Stem cell therapy has emerged as a transformative approach in maxillofacial surgery, offering novel solutions for the regeneration of bone and soft tissues lost due to trauma, congenital anomalies, infection, or tumor resection. Stem cell therapy has emerged as a promising alternative, leveraging the potential of mesenchymal stem cells (MSCs), adipose-derived stem cells (ADSCs), oral-derived stem cells, and induced pluripotent stem cells (iPSCs). These cells exhibit remarkable multipotency, immunomodulatory properties, and capacity for tissue repair. Clinical and preclinical studies demonstrate that stem cell-based therapies—especially when combined with advanced biomaterials and scaffolds—can enhance bone regeneration, improve vascularization, and reduce complications compared to conventional grafting. Dental-derived MSCs, in particular, are gaining traction due to their accessibility and strong regenerative potential. Despite promising results, challenges remain regarding standardization of protocols, long-term safety, and regulatory approval. This review critically examines the sources, mechanisms, clinical applications, and future directions of stem cell therapy in maxillofacial surgery, highlighting the convergence of biotechnology, regenerative medicine, and tissue engineering in advancing patient care.

Anahtar Kelimeler

• Stem cell therapy
• Maxillofacial surgery
• Bone regeneration
• Mesenchymal stem cells
• Regenerative medicine.

Maksillofasiyal Cerrahide Kök Hücre Tedavisi: Bir Literatür İncelemesi

Öz

Kök hücre tedavisi, travma, konjenital anomaliler, enfeksiyon veya tümör rezeksiyonu nedeniyle kaybedilen kemik ve yumuşak dokuların rejenerasyonu için yeni çözümler sunan maksillofasiyal cerrahide dönüştürücü bir yaklaşım olarak ortaya çıkmıştır. Kök hücre tedavisi, mezenkimal kök hücrelerin (MSC'ler), yağdan türetilen kök hücrelerin (ADSC'ler), oral kaynaklı kök hücrelerin ve indüklenmiş pluripotent kök hücrelerin (iPSC'ler) potansiyelinden yararlanan umut verici bir alternatif olarak ortaya çıkmıştır. Bu hücreler, dikkate değer çok yönlülük, immünomodülatör özellikler ve doku onarımı kapasitesi sergiler. Klinik ve klinik öncesi çalışmalar, kök hücre bazlı tedavilerin, özellikle gelişmiş biyomalzemeler ve iskelelerle birleştirildiğinde, geleneksel greftlemeye kıyasla kemik rejenerasyonunu artırabileceğini, vaskülarizasyonu iyileştirebileceğini ve komplikasyonları azaltabileceğini göstermektedir. Özellikle diş kaynaklı MSC'ler, erişilebilirlikleri ve güçlü rejeneratif potansiyelleri nedeniyle ilgi görmektedir. Umut verici sonuçlara rağmen, protokollerin standardizasyonu, uzun vadeli güvenlik ve düzenleyici onay konusunda zorluklar devam etmektedir. Bu inceleme, maksillofasiyal cerrahide kök hücre tedavisinin kaynaklarını, mekanizmalarını, klinik uygulamalarını ve gelecekteki yönlerini eleştirel bir şekilde inceleyerek, hasta bakımının ilerlemesinde biyoteknoloji, rejeneratif tıp ve doku mühendisliğinin bir araya gelişini vurgulamaktadır.

Anahtar Kelimeler

• Kök hücre tedavisi
• Maksillofasiyal cerrahi
• Kemik rejenerasyonu
• Mezenkimal kök hücreler
• Rejeneratif tıp.

Kaynakça

1. 1. Tahmasebi E, Mohammadi M, Alam M, Abbasi K, Gharibian Bajestani S, Khanmohammad R, et al. The current regenerative medicine approaches of craniofacial diseases: A narrative review. Front Cell Dev Biol. 2023;11:1112378.
2. 2. Iyer S, Thankappan K. Maxillary reconstruction: Current concepts and controversies. Indian J Plast Surg. 2014;47(1):8.
3. 3. Powcharoen W, Yang WF, Li KY, Zhu W, Su YX. Computer-assisted versus conventional freehand mandibular reconstruction with fibula free flap: A systematic review and meta-analysis. Plast Reconstr Surg. 2019;144(6):1417-28.
4. 4. Nauth A, Schemitsch E, Norris B, Nollin Z, Watson JT. Critical-size bone defects: Is there a consensus for diagnosis and treatment? J Orthop Trauma. 2018;32:S7-11.
5. 5. Hollý D, Klein M, Mazreku M, Zamborský R, Polák Š, Danišovič Ľ, et al. Stem cells and their derivatives: Implications for alveolar bone regeneration. Int J Mol Sci. 2021;22(21):11746.
6. 6. Chaparro O, Linero I. Regenerative medicine: A new paradigm in bone regeneration. Adv Tech Bone Regen. 2016;12:253-74.
7. 7. Wu V, Helder MN, Bravenboer N, Ten Bruggenkate CM, Jin J, Klein-Nulend J, et al. Bone tissue regeneration in the oral and maxillofacial region: A review on stem cells and new strategies for vascularization. Stem Cells Int. 2019;2019:6279721.
8. 8. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143-7.

9. 9. Machado E, Fernandes MH, de Sousa Gomes P. Dental stem cells for craniofacial tissue engineering. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;113(6):728-33.
10. 10. Langer R, Vacanti JP. Tissue engineering. Science. 1993;260(5110):920-6.
11. 11. Gundu S, Varshney N, Sahi AK, Mahto SK. Recent developments in biomaterial scaffolds and regenerative approaches for craniomaxillofacial bone tissue engineering. J Polym Res. 2022;29(3):73.
12. 12. Fitzpatrick V, Martín-Moldes Z, Deck A, Torres-Sanchez R, Valat A, Cairns D, et al. Functionalized 3D-printed silk-hydroxyapatite scaffolds for enhanced bone regeneration with innervation and vascularization. Biomaterials. 2021;276:120995.
13. 13. Nair MA, Shaik KV, Kokkiligadda A, Gorrela H. Tissue-engineered maxillofacial skeletal defect reconstruction by 3D-printed β-TCP scaffold with growth factors and MSCs. J Med Life. 2020;13(3):418.
14. 14. Zhuang Y, Cheng M, Li M, Cui J, Huang J, Zhang C, et al. Small extracellular vesicles from hypoxic MSCs promote vascularized bone regeneration via miR-210-3p/EFNA3/PI3K pathway. Acta Biomater. 2022;150:413-26.
15. 15. Paz AG, Maghaireh H, Mangano FG. Stem cells in dentistry: Types and clinical applications. Stem Cells Int. 2018;2018:4313610.
16. 16. Spagnuolo G, Codispoti B, Marrelli M, Rengo C, Rengo S, Tatullo M. Commitment of oral-derived stem cells in dental and maxillofacial applications. Dent J. 2018;6(4):72.
17. 17. Gjerde C, Mustafa K, Hellem S, Rojewski M, Gjengedal H, Yassin MA, et al. Cell therapy-induced regeneration of severely atrophied mandibular bone in a clinical trial. Stem Cell Res Ther. 2018;9:1-5.
18. 18. Kaigler D, Avila-Ortiz G, Travan S, Taut AD, Padial-Molina M, Rudek I, et al. Bone engineering of maxillary sinus defects using enriched CD90+ stem cells: A randomized clinical trial. J Bone Miner Res. 2015;30(7):1206-16.
19. 19. Naderi N, Griffin MF, Mosahebi A, Butler PE, Seifalian AM. Adipose-derived stem cells and platelet-rich plasma improve integration and angiogenesis of biodegradable scaffolds. Mol Biol Rep. 2020;47:2005-13.
20. 20. Chalisserry EP, Nam SY, Park SH, Anil S. Therapeutic potential of dental stem cells. J Tissue Eng. 2017;8:2041731417702531.
21. 21. Tatullo M, Codispoti B, Paduano F, Nuzzolese M, Makeeva I. Strategic tools in regenerative and translational dentistry. Int J Mol Sci. 2019;20(8):1879.
22. 22. Fliefel R, Ehrenfeld M, Otto S. Induced pluripotent stem cells (iPSCs) as a new source of bone: A systematic review and meta-analysis. J Tissue Eng Regen Med. 2018;12(7):1780-97.
23. 23. Xian D, Shen LH, Yi Z, He LH. Exosomes from adipose-derived stem cells prevent MRONJ. Med Sci Monit. 2021;27:e929684.
24. 24. Iaquinta MR, Mazzoni E, Manfrini M, D’Agostino A, Trevisiol L, Nocini R, et al. Innovative biomaterials for bone regrowth. Int J Mol Sci. 2019 Jan 31;20(3):618.
25. 25. Huang X, Lou Y, Duan Y, Liu H, Tian J, Shen Y, Wei X. Biomaterial scaffolds in maxillofacial bone tissue engineering: Recent advances. Bioact Mater. 2024;33:129-56.
26. 26. Saberian E, Jenča A, Zafari Y, Jenča A, Petrášová A, Zare-Zardini H, et al. Scaffold application for bone regeneration with stem cells in dentistry: A review. Cells. 2024;13(12):1065.
27. 27. Purbantoro SD, Taephatthanasagon T, Purwaningrum M, Hirankanokchot T, Peralta S, Fiani N, et al. Trends of regenerative tissue engineering for oral and maxillofacial reconstruction in veterinary medicine. Front in Vet Sci. 2024 Feb 21;11:1325559.
28. 28. Malzoni CM, Oliveira JA, Soares LF, Chimirri MC, Almeida DA, Pigossi SC, et al. 3D-printed bioresorbable scaffolds for maxillofacial bone reconstruction: A scoping review. Braz Dent J. 2024;35:e24-6112.
29. 29. Liu P, Zhang Y, Ma Y, Tan S, Ren B, Liu S, et al. Dental pulp stem cells in maxillofacial tissue engineering. Int J Med Sci. 2022;19(2):310.
30. 30. Zakrzewski W, Dobrzynski M, Rybak Z, Szymonowicz M, Wiglusz RJ. Nanomaterials with stem cells for alveolar bone regeneration. Nanomaterials. 2020;10(6):1216.
31. 31. Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells in vitro and in vivo. Proc Natl Acad Sci USA. 2000;97(25):13625-30.
32. 32. Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG, et al. SHED: Stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci USA. 2003;100(10):5807-12.
33. 33. Luby AO, Ranganathan K, Lynn JV, Nelson NS, Donneys A, Buchman SR. Stem cells for bone regeneration: Current state and future directions. J Craniofac Surg. 2019;30(3):730-5.
34. 34. Zhao Y, Xie L. Mesenchymal stem cell-centered therapies in TMJ osteoarthritis: An update. Stem Cells Int. 2021;2021:6619527.
35. 35. Cui D, Li H, Xu X, Ye L, Zhou X, Zheng L, et al. MSCs for TMJ cartilage regeneration. Stem Cells Int. 2017;2017:5979741.
36. 36. Matheus HR, Özdemir ŞD, Guastaldi FP. Stem cell-based therapies for TMJ osteoarthritis: A systematic review. Osteoarthritis Cartilage. 2022;30(9):1174-85.
37. 37. Minervini G, Del Mondo D, Russo D, Cervino G, D’Amico C, Fiorillo L. Stem cells in TMJ engineering: Current perspectives. J Craniofac Surg. 2022;33(7):2181-7.
38. 38. Gong S, Emperumal CP, Al-Eryani K, Enciso R. TMJ regeneration using in vitro human stem cells. J Tissue Eng Regen Med. 2022;16(7):591-604.
39. 39. Zhang S, Yap AU, Toh WS. Stem cells for TMJ repair and regeneration. Stem Cell Rev Rep. 2015;11:728-42.
40. 40. Yi P, Liang J, Huang F, Zhao Z, Zhou X, Gao Q, et al. Composite 3D-printed polymer and acellular matrix hydrogel for TMJ disc repair. Front Mater. 2021;8:621416.
41. 41. Gundestrup AK, Lynggaard CD, Forner L, et al. MSC therapy for osteoradionecrosis of the mandible: Systematic review. Stem Cell Rev Rep. 2020;16:1208-21.
42. 42. On SW, Cho SW, Byun SH, Yang BE. Therapeutic approaches for MRONJ: A narrative review. Antioxidants. 2021;10(5):680.
43. 43. Yang Y, Lin S, Wang B, Gu W, Li G. Stem cell therapy for distraction osteogenesis: A review. Bone Joint Res. 2017;6(6):385-90.
44. 44. Jia Y, Zhu Y, Qiu S, Xu J, Chai Y. Exosomes from EPCs accelerate bone regeneration during distraction osteogenesis. Stem Cell Res Ther. 2019;10:1-3.
45. 45. Kidd S, Spaeth E, Dembinski JL, Dietrich M, Watson K, Klopp A, et al. Mesenchymal stem cell tropism for tumor and wound microenvironments in vivo. Stem Cells. 2009;27(10):2614-23.
46. 46. Kauer TM, Figueiredo JL, Hingtgen S, Shah K. Encapsulated therapeutic stem cells induce glioma cell death. Nat Neurosci. 2012;15(2):197-204.
47. 47. Waterman RS, Tomchuck SL, Henkle SL, Betancourt AM. MSC1 or MSC2 polarization paradigm. PLoS One. 2010;5(4):e10088.
48. 48. Sun Q, Chen X, Luo H, Meng C, Zhu D. Cancer stem cells of head and neck SCC: A systematic review. Am J Cancer Res. 2023;13(9):4315.
49. 49. Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007 Oct 4;449(7162):557-63.
50. 50. Studeny M, Marini FC, Champlin RE, Zompetta C, Fidler IJ, Andreeff M. MSCs as vehicles for IFN-β delivery into tumors. Cancer Res. 2002;62(13):3603-8.
51. 51. Kim N, Cho SG. Clinical applications of MSCs. Korean J Intern Med. 2013;28(4):387-402.