Impact of patients-derived stem cells from exfoliated deciduous teeth on the pathogenesis and a novel therapeutics for biliary atresia.

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18945
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Kyushu University
• Principal Investigator: Sondoa Soichiro 九州大学, 歯学研究院, 助教 (10831985)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 乳歯幹細胞 / 胆道閉鎖症 / エピジェネティクス

Outline of Final Research Achievements

Biliary atresia (BA) is a cholestatic disease caused by bile duct obstruction. In some cases, BA patients get hepatic fibrosis. In this study, we isolated stem cells from exfoliated deciduous teeth of healthy donors (SHED) and BA patients (BA-SHED). Then we examined the stem cell properties of and therapeutic effects of transplantation of SHED and BA-SHED. BA-SHED expressed higher levels of HNF6 and lower levels of Transforming growth factor-beta receptor (TGFBR), which is important for differentiation of cholangiocyte. Downregulation of HNF6 expression in BA-SHED ameliorated TGFBR expression. These results indicate that downregulation of HNF6 in BA-SHED is a possible cell processing method for autologous transplantation of BA-SHED.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

胆道閉鎖症は新生児期に発症する難知性の疾患であり、その原因は不明である。胆管の閉鎖による胆汁のうっ滞を呈するため、胆汁の流路を形成する外科手術が行われるが、手術が奏功しない症例も多く、最終的に肝移植が必要になる。しかし、小児に移植可能な肝臓ドナーは限られており、移植待機中の肝線維化を抑制する方法が望まれる。本研究の成果は、胆道閉鎖症患者由来の乳歯幹細胞を肝線維症に対する自家細胞移植の細胞ソースとして用いるための学術的基盤を提示することに学術的・社会的意義がある。