Tissue Eng Regen Med.
2020 Feb;17(1):105-119. 10.1007/s13770-019-00226-7.
Wound Healing Promoting Activity of Tonsil-Derived Stem Cells on 5-Fluorouracil-Induced Oral Mucositis Model
- Affiliations
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- 1Institute of New Frontier Research Team, Hallym University, Hallym Clinical and Translation Science Institute, 1 Hallymdaehak-gil, Chuncheon, Gangwon-do, 24252, Republic of Korea
- 2Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Ewha Womans University, 1071 Anyangcheon-ro, Seoul, 07985, Republic of Korea
- 3Department of Otorhinolaryngology–Head and Neck Surgery, College of Medicine, Chuncheon Sacred Heart Hospital, Hallym University, 77 Sakju-ro, Chuncheon, Gangwon-do, 24253, Republic of Korea
- 4Department of Anesthesiology and Pain Medicine, College of Medicine, Hallym University, 77 Sakju-ro, Chuncheon, Gangwon-do, 24253, Republic of Korea
- KMID: 2509258
- DOI: http://doi.org/10.1007/s13770-019-00226-7
Abstract
- Background
We first determined the efficacy of lesional injection of tonsil-derived MSCs (mesenchymal stem cells) for the treatment of 5-fluorouracil induced oral mucositis.
Methods
Oral mucositis was induced in hamsters by administration of 5-fluorouracil (day 0, 2, 4) followed by mechanical trauma (day 1, 2, 4). The experimental groups included MT (mechanical trauma only), 5-FU + MT (mechanical trauma with 5-fluorouracil administration), TMSC (mechanical trauma with 5-fluorouracil administration, tonsil-derived mesenchymal stem cells injection), DEXA (mechanical trauma with 5-fluorouracil administration, dexamethasone injection), and saline (mechanical trauma with 5-fluorouracil administration, saline injection).
Results
On day 10, gross and histologic analyses showed that nearly complete healing and epithelialization of the cheek mucosa of the TMSC group, whereas the other groups showed definite ulcerative lesions. Compared with the MT and DEXA groups, CD31 expression was greater in the TMSC group on days 10 and 14. Tendency towards a decrease in MMP2 expression with the time in the TMSC group was observed. In addition, the TMSC group showed higher expression of TGF-β, and NOX4 on day 10 compared with the other groups. Scratch assay demonstrated that the conditioned media harvested from tonsil-derived MSCs significantly increased migratory efficacy of NIH3T3 cells. Transwell assay showed that the preferential migration of tonsil-derived MSCs to the wound area.
Conclusion
Intralesional administration of tonsil-derived MSCs may accelerate wound healing of 5-fluorouracil induced oral mucositis by upregulating neovascularization and effective wound contraction. In addition, tonsil-derived MSCs might contribute to oral ulcer regeneration via the stimulation of fibroblast proliferation and migration.
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