Potential effect of the stem cell therapy on drug-induced anomalies of tooth root.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K17344
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Fukuoka Dental College
• Principal Investigator: Nakamura Masako 福岡歯科大学, 口腔歯学部, 助教 (70781102)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 小児悪性腫瘍 / シクロホスファミド / Hertwig's上皮鞘 / 上皮間葉形質転換

Outline of Final Research Achievements

Chemotherapy with higher doses causes dental anomalies, such as hypodontia, microdontia, and atypical root formation, in children with malignant tumors.
This study examined whether potential harmful effect of cyclophosphamide (CPA) on tooth development leads to atypical root formation in mice. Mice treated with higher doses of CPA showed an arrested root development due to early apical foramen closure. Hertwig’s root sheath cell line (HERS) cells cultured with higher doses of CPA revealed decreased expression of E-cadherin, while N-cadherin expression was upregulated, indicating that this cadherin switch may facilitate an epithelial-to-mesenchymal transition (EMT)-like phenomenon. These findings suggest that administration of high doses of CPA can lead to arrest in root development, due to EMT of HERS cells during root development.

Free Research Field

小児歯科学

Academic Significance and Societal Importance of the Research Achievements

小児癌治療によって歯の形成が停止した小児に対しては、暫間義歯などの補綴修復物による限られた対応しかできない。しかし、抗がん剤治療による歯の形成不全メカニズムが解明できれば、抗がん剤投与後の歯の萌出異常などの晩発障害に対し新たな対応を提案できると考えた。本研究課題では、抗がん剤投与マウスを作製し、抗がん剤治療による短根化メカニズムの一端を明らかにした。これらの成果は、乳歯列・混合歯列期に抗がん剤治療を受ける小児に対し、晩発障害を小さくできる可能性を高めるとともに歯の再生研究への基礎研究にもなり得る。