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

Harry Jung; Han Su Kim; Jun Ho Lee; Jae Jun Lee; Hae Sang Park

doi:10.1007/s13770-019-00226-7

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

Harry Jung, Han Su Kim, Jun Ho Lee, Jae Jun Lee, Hae Sang Park

Department of Otolaryngology

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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.

Original language	English
Pages (from-to)	105-119
Number of pages	15
Journal	Tissue Engineering and Regenerative Medicine
Volume	17
Issue number	1
DOIs	https://doi.org/10.1007/s13770-019-00226-7
State	Published - 1 Feb 2020

Bibliographical note

Funding Information:
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.

Funding Information:
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.

Publisher Copyright:
© 2019, The Korean Tissue Engineering and Regenerative Medicine Society.

Keywords

Mechanical trauma
Oral mucositis
Stem cells
Tonsil
Wound healing

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10.1007/s13770-019-00226-7

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

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.",

keywords = "Mechanical trauma, Oral mucositis, Stem cells, Tonsil, Wound healing",

author = "Harry Jung and Kim, {Han Su} and Lee, {Jun Ho} and Lee, {Jae Jun} and Park, {Hae Sang}",

note = "Funding Information: 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. Funding Information: 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. Publisher Copyright: {\textcopyright} 2019, The Korean Tissue Engineering and Regenerative Medicine Society.",

year = "2020",

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doi = "10.1007/s13770-019-00226-7",

language = "English",

volume = "17",

pages = "105--119",

journal = "Tissue Engineering and Regenerative Medicine",

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publisher = "Springer Science + Business Media",

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T1 - Wound Healing Promoting Activity of Tonsil-Derived Stem Cells on 5-Fluorouracil-Induced Oral Mucositis Model

AU - Jung, Harry

AU - Kim, Han Su

AU - Lee, Jun Ho

AU - Lee, Jae Jun

AU - Park, Hae Sang

N1 - Funding Information: 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. Funding Information: 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. Publisher Copyright: © 2019, The Korean Tissue Engineering and Regenerative Medicine Society.

PY - 2020/2/1

Y1 - 2020/2/1

N2 - 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.

AB - 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.

KW - Mechanical trauma

KW - Oral mucositis

KW - Stem cells

KW - Tonsil

KW - Wound healing

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U2 - 10.1007/s13770-019-00226-7

DO - 10.1007/s13770-019-00226-7

M3 - Article

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SN - 1738-2696

VL - 17

SP - 105

EP - 119

JO - Tissue Engineering and Regenerative Medicine

JF - Tissue Engineering and Regenerative Medicine

IS - 1

ER -

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

Abstract

Bibliographical note

Keywords

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