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Wound Healing Promoting Activity of Tonsil-Derived Stem Cells on 5-Fluorouracil-Induced Oral Mucositis Model

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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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Acknowledgements

This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science, Information and Communication Technologies and Future Planning of the Korea government (NRF-2017M3A9E8033206); the National Research Foundation of Korea (NRF) grant funded by the Korea government (NRF-2017R1D1A1B04034145); the Hallym University Research Fund.

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Correspondence to Hae Sang Park.

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The authors declare that they have no conflict of interest.

Ethical statement

Informed written consent was obtained from the legal guardians of all patients who participated in this study, and the study protocol was approved by the institutional review board of Hallym University Medical Center (2016-41). The animal studies were performed after receiving approval of the Institutional review board of Hallym University (Hallym 2018-67), Chuncheon, Republic of Korea.

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Jung, H., Kim, H.S., Lee, J.H. et al. Wound Healing Promoting Activity of Tonsil-Derived Stem Cells on 5-Fluorouracil-Induced Oral Mucositis Model. Tissue Eng Regen Med (2019). https://doi.org/10.1007/s13770-019-00226-7

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Keywords

  • Stem cells
  • Tonsil
  • Oral mucositis
  • Wound healing
  • Mechanical trauma