Mesenchymal Stem Cell Therapy for Oral Lichen Planus: A Paradigm Shift from Palliation to Regeneration?
-
Shahabodin Babaeifard
,
Mohaddese Marzban
,
Ghazaleh Kheiri
,
Leyla Sharifi Aliabadi
,
Ghazal Razani
,
Maryam Barkhordar
Abstract
Oral lichen planus (OLP) is a chronic, T-cell-mediated inflammatory disease of the oral mucosa, notable for its symptomatic burden and potential for malignant transformation. While corticosteroids and immunosuppressants remain the standard of care, their transient efficacy and adverse effect profile underscore a significant unmet clinical need. Mesenchymal stem cells (MSCs), with their multifaceted immunomodulatory and regenerative capabilities, are emerging as a compelling therapeutic alternative. This editorial synthesizes current evidence, positing that MSCs can fundamentally disrupt the immunopathogenic cycle of OLP. We explore the mechanisms by which MSCs re-establish immune tolerance and promote tissue repair, and we critically assess the translational pathway from preclinical models to clinical application. Despite promising results, the journey to clinical adoption necessitates overcoming hurdles in standardization, delivery, and safety profiling. We argue that MSC-based therapy represents not merely an incremental improvement, but a potential paradigm shift towards a curative strategy for this recalcitrant disease.
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2. Nukaly HY, Halawani IR, Alghamdi SMS, et al. Oral Lichen Planus: A Narrative Review Navigating Etiologies, Clinical Manifestations, Diagnostics, and Therapeutic Approaches. J Clin Med. 2024;13(17):5280.
3. El-Howati A, Thornhill MH, Colley HE, et al. Immune mechanisms in oral lichen planus. Oral Dis. 2023;29(4):1400–15.
4. Hassan AAA, Elgendi M, Shaker O, et al. Salivary level of interleukin-17 in patients having atrophic and erosive oral lichen planus before and after treatment with topical steroids (A Controlled clinical trial). Egypt Dent J. 2021;67(1):379–85.
5. Dvorak G, Monshi B, Hof M, et al. Gender aspects in oral health-related quality of life of oral lichen planus patients. Int J Stomatol Occlusion Med. 2015;8(2):33-40.
6. Monteiro BV, Pereira Jdos S, Nonaka CF, et al. Immunoexpression of Th17-related cytokines in oral lichen planus. Appl Immunohistochem Mol Morphol. 2015;23(6):409–15.
7. Parashar P. Oral lichen planus. Otolaryngol Clin North Am. 2011;44(1):89–107, vi.
8. Sugerman PB, Savage NW, Walsh LJ, et al. The pathogenesis of oral lichen planus. Crit Rev Oral Biol Med. 2002;13(4):350–65.
9. Scully C, Carrozzo M. Oral mucosal disease: Lichen planus. Br J Oral Maxillofac Surg. 2008;46(1):15–21.
10. Srinivas K, Aravinda K, Ratnakar P, et al. Oral lichen planus - Review on etiopathogenesis. Natl J Maxillofac Surg. 2011;2(1):15–6.
11. El-Refai I, Maged A, El-Saady D. Assessment of IL-17 in Oral Lichen Planus and in Pemphigus Vulgaris. Egypt Dent J. 2019;65(1):343–50.
12. Lodi G, Scully C, Carrozzo M, et al. Current controversies in oral lichen planus: report of an international consensus meeting. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100(2):164-78.
13. Farhi D, Dupin N. Pathophysiology, etiologic factors, and clinical management of oral lichen planus, part I: facts and controversies. Clin Dermatol. 2010;28(1):100–8.
14. Chen E, Sami N. Systemic tacrolimus in the treatment of recalcitrant mucosal lichen planus. JAAD Case Rep. 2017;3(3):253–5.
15. Ficarra G, Flaitz CM, Gaglioti D, et al. White lichenoid lesions of the buccal mucosa in patients with HIV infection. Oral Surg Oral Med Oral Pathol. 1993;76(4):460-6.
16. Kim RH, Mehrazarin S, Kang MK. Therapeutic potential of mesenchymal stem cells for oral and systemic diseases. Dent Clin North Am. 2012;56(3):651–75.
17. Zhang Q, Nguyen AL, Shi S, et al. Three-dimensional spheroid culture of human gingiva-derived mesenchymal stem cells enhances mitigation of chemotherapy-induced oral mucositis. Stem Cells Dev. 2012;21(6):937–47.
18. Wu Y, Chen L, Scott PG, et al. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells. 2007;25(10):2648–59.
19. El-Menoufy H, Aly LA, Aziz MT, et al. The role of bone marrow-derived mesenchymal stem cells in treating formocresol induced oral ulcers in dogs. J Oral Pathol Med. 2010;39(4):281–9.
20. Aziz Aly LA, Menoufy HE, Ragae A, et al. Adipose stem cells as alternatives for bone marrow mesenchymal stem cells in oral ulcer healing. Int J Stem Cells. 2012;5(2):104–14.
21. Shaker O, Hassan AS. Possible role of interleukin‐17 in the pathogenesis of lichen planus. Br J Dermatol. 2012;166(6):1367–8.
22. Ding G, Wang W, Liu Y, et al. Mesenchymal stem cell transplantation: a potential therapy for oral lichen planus. Med Hypotheses. 2011;76(3):322–4.
23. Ryu HS, Abueva C, Padalhin A, et al. Oral ulcer treatment using human tonsil-derived mesenchymal stem cells encapsulated in trimethyl chitosan hydrogel: an animal model study. Stem Cell Res Ther. 2024;15(1):103.
24. Ghanaati H, Rouzbahani M, Golzarian J, et al. Genicular Artery Embolization Using Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis: A Prospective Study. J Vasc Interv Radiol. 2025;36(10):1523-1531.e1.
25. Saleh M, Vaezi AA, Sohrabpour AA, et al. Wharton's jelly-mesenchymal stem cells treatment for severe COVID 19 patients: 1-year follow-up. Gene Rep. 2022;29:101691.
26. Shi S, Gronthos S. Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J Bone Miner Res. 2003;18(4):696–704.
27. Huang M, Huang Y, Liu H, et al. Hydrogels for the treatment of oral and maxillofacial diseases: current research, challenges, and future directions. Biomater Sci. 2022;10(22):6413–46.
28. Zhou Ll, Liu W, Wu Ym, et al. Oral Mesenchymal Stem/Progenitor Cells: The Immunomodulatory Masters. Stem Cells Int. 2020;2020:1327405.
29. Li J, Wu Z, Zhao L, et al. The heterogeneity of mesenchymal stem cells: an important issue to be addressed in cell therapy. Stem Cell Res Ther. 2023;14(1):381.
30. Lalu MM, McIntyre L, Pugliese C, et al. Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One. 2012;7(10):e47559.
31. Song SJ, Nam Y, Rim YA, et al. Comparative analysis of regulations and studies on stem cell therapies: focusing on induced pluripotent stem cell (iPSC)-based treatments. Stem Cell Res Ther. 2024;15(1):447.
32. Wei L, Yan W, Shah W, et al. Advancements and challenges in stem cell transplantation for regenerative medicine. Heliyon. 2024;10(16):e35836.
33. Műzes G, Sipos F. Mesenchymal stem cell-derived secretome: a potential therapeutic option for autoimmune and immune-mediated inflammatory diseases. Cells. 2022;11(15):2300.
34. Keshtkar S, Azarpira N, Ghahremani MH. Mesenchymal stem cell-derived extracellular vesicles: novel frontiers in regenerative medicine. Stem Cell Res Ther. 2018;9(1):63.
35. Hazrati A, Malekpour K, Soudi S, et al. CRISPR/Cas9-engineered mesenchymal stromal/stem cells and their extracellular vesicles: A new approach to overcoming cell therapy limitations. Biomed Pharmacother. 2022;156:113943.
36. Carp DM, Liang Y. Universal or Personalized Mesenchymal Stem Cell Therapies: Impact of Age, Sex, and Biological Source. Cells. 2022;11(13):2077.
2. Nukaly HY, Halawani IR, Alghamdi SMS, et al. Oral Lichen Planus: A Narrative Review Navigating Etiologies, Clinical Manifestations, Diagnostics, and Therapeutic Approaches. J Clin Med. 2024;13(17):5280.
3. El-Howati A, Thornhill MH, Colley HE, et al. Immune mechanisms in oral lichen planus. Oral Dis. 2023;29(4):1400–15.
4. Hassan AAA, Elgendi M, Shaker O, et al. Salivary level of interleukin-17 in patients having atrophic and erosive oral lichen planus before and after treatment with topical steroids (A Controlled clinical trial). Egypt Dent J. 2021;67(1):379–85.
5. Dvorak G, Monshi B, Hof M, et al. Gender aspects in oral health-related quality of life of oral lichen planus patients. Int J Stomatol Occlusion Med. 2015;8(2):33-40.
6. Monteiro BV, Pereira Jdos S, Nonaka CF, et al. Immunoexpression of Th17-related cytokines in oral lichen planus. Appl Immunohistochem Mol Morphol. 2015;23(6):409–15.
7. Parashar P. Oral lichen planus. Otolaryngol Clin North Am. 2011;44(1):89–107, vi.
8. Sugerman PB, Savage NW, Walsh LJ, et al. The pathogenesis of oral lichen planus. Crit Rev Oral Biol Med. 2002;13(4):350–65.
9. Scully C, Carrozzo M. Oral mucosal disease: Lichen planus. Br J Oral Maxillofac Surg. 2008;46(1):15–21.
10. Srinivas K, Aravinda K, Ratnakar P, et al. Oral lichen planus - Review on etiopathogenesis. Natl J Maxillofac Surg. 2011;2(1):15–6.
11. El-Refai I, Maged A, El-Saady D. Assessment of IL-17 in Oral Lichen Planus and in Pemphigus Vulgaris. Egypt Dent J. 2019;65(1):343–50.
12. Lodi G, Scully C, Carrozzo M, et al. Current controversies in oral lichen planus: report of an international consensus meeting. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100(2):164-78.
13. Farhi D, Dupin N. Pathophysiology, etiologic factors, and clinical management of oral lichen planus, part I: facts and controversies. Clin Dermatol. 2010;28(1):100–8.
14. Chen E, Sami N. Systemic tacrolimus in the treatment of recalcitrant mucosal lichen planus. JAAD Case Rep. 2017;3(3):253–5.
15. Ficarra G, Flaitz CM, Gaglioti D, et al. White lichenoid lesions of the buccal mucosa in patients with HIV infection. Oral Surg Oral Med Oral Pathol. 1993;76(4):460-6.
16. Kim RH, Mehrazarin S, Kang MK. Therapeutic potential of mesenchymal stem cells for oral and systemic diseases. Dent Clin North Am. 2012;56(3):651–75.
17. Zhang Q, Nguyen AL, Shi S, et al. Three-dimensional spheroid culture of human gingiva-derived mesenchymal stem cells enhances mitigation of chemotherapy-induced oral mucositis. Stem Cells Dev. 2012;21(6):937–47.
18. Wu Y, Chen L, Scott PG, et al. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells. 2007;25(10):2648–59.
19. El-Menoufy H, Aly LA, Aziz MT, et al. The role of bone marrow-derived mesenchymal stem cells in treating formocresol induced oral ulcers in dogs. J Oral Pathol Med. 2010;39(4):281–9.
20. Aziz Aly LA, Menoufy HE, Ragae A, et al. Adipose stem cells as alternatives for bone marrow mesenchymal stem cells in oral ulcer healing. Int J Stem Cells. 2012;5(2):104–14.
21. Shaker O, Hassan AS. Possible role of interleukin‐17 in the pathogenesis of lichen planus. Br J Dermatol. 2012;166(6):1367–8.
22. Ding G, Wang W, Liu Y, et al. Mesenchymal stem cell transplantation: a potential therapy for oral lichen planus. Med Hypotheses. 2011;76(3):322–4.
23. Ryu HS, Abueva C, Padalhin A, et al. Oral ulcer treatment using human tonsil-derived mesenchymal stem cells encapsulated in trimethyl chitosan hydrogel: an animal model study. Stem Cell Res Ther. 2024;15(1):103.
24. Ghanaati H, Rouzbahani M, Golzarian J, et al. Genicular Artery Embolization Using Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis: A Prospective Study. J Vasc Interv Radiol. 2025;36(10):1523-1531.e1.
25. Saleh M, Vaezi AA, Sohrabpour AA, et al. Wharton's jelly-mesenchymal stem cells treatment for severe COVID 19 patients: 1-year follow-up. Gene Rep. 2022;29:101691.
26. Shi S, Gronthos S. Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J Bone Miner Res. 2003;18(4):696–704.
27. Huang M, Huang Y, Liu H, et al. Hydrogels for the treatment of oral and maxillofacial diseases: current research, challenges, and future directions. Biomater Sci. 2022;10(22):6413–46.
28. Zhou Ll, Liu W, Wu Ym, et al. Oral Mesenchymal Stem/Progenitor Cells: The Immunomodulatory Masters. Stem Cells Int. 2020;2020:1327405.
29. Li J, Wu Z, Zhao L, et al. The heterogeneity of mesenchymal stem cells: an important issue to be addressed in cell therapy. Stem Cell Res Ther. 2023;14(1):381.
30. Lalu MM, McIntyre L, Pugliese C, et al. Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One. 2012;7(10):e47559.
31. Song SJ, Nam Y, Rim YA, et al. Comparative analysis of regulations and studies on stem cell therapies: focusing on induced pluripotent stem cell (iPSC)-based treatments. Stem Cell Res Ther. 2024;15(1):447.
32. Wei L, Yan W, Shah W, et al. Advancements and challenges in stem cell transplantation for regenerative medicine. Heliyon. 2024;10(16):e35836.
33. Műzes G, Sipos F. Mesenchymal stem cell-derived secretome: a potential therapeutic option for autoimmune and immune-mediated inflammatory diseases. Cells. 2022;11(15):2300.
34. Keshtkar S, Azarpira N, Ghahremani MH. Mesenchymal stem cell-derived extracellular vesicles: novel frontiers in regenerative medicine. Stem Cell Res Ther. 2018;9(1):63.
35. Hazrati A, Malekpour K, Soudi S, et al. CRISPR/Cas9-engineered mesenchymal stromal/stem cells and their extracellular vesicles: A new approach to overcoming cell therapy limitations. Biomed Pharmacother. 2022;156:113943.
36. Carp DM, Liang Y. Universal or Personalized Mesenchymal Stem Cell Therapies: Impact of Age, Sex, and Biological Source. Cells. 2022;11(13):2077.
| Files | ||
| Issue | Vol 20 No 1 (2026): Articles In Press | |
| Section | Editorial | |
| Keywords | ||
| Oral lichen planus; Mesenchymal stem cells; Immunomodulation; Regenerative medicine; Cell therapy; Autoimmune disease | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Babaeifard S, Marzban M, Kheiri G, Sharifi Aliabadi L, Razani G, Barkhordar M. Mesenchymal Stem Cell Therapy for Oral Lichen Planus: A Paradigm Shift from Palliation to Regeneration?. Int J Hematol Oncol Stem Cell Res. 2026;20(1).
