Cell Therapy Development for Congenital Metabolic Diseases Using Human Amniotic Epithelial Cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17522
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Nihon University
• Principal Investigator: TAKANO Chika 日本大学, 医学部, 助教 (50845310)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 羊膜上皮細胞 / 多能性幹細胞 / 先天性代謝異常症 / 上皮間葉転換 / TGF-β経路

Outline of Final Research Achievements

Human amniotic epithelial cells (hAECs), which are a type of placental stem cell, express stem cell marker genes and are capable of differentiating into all three germ layers under appropriate culture conditions. hAECs are known to undergo TGF-β-dependent epithelial-mesenchymal transition (EMT); however, the impact of EMT on the stemness or differentiation of hAECs has not yet been determined. Here, we first confirmed that hAECs undergo EMT immediately after starting primary culture. Comprehensive transcriptome analysis using RNA-seq revealed that inhibition of TGF-β-dependent EMT maintained the expression of stemness-related genes, including NANOG and POU5F1, in hAECs. Moreover, the maintenance of stemness did not affect the nontumorigenic characteristics of hAECs. We showed for the first time that TGF-β-dependent EMT negatively affected the stemness of hAECs, providing novel insight into cellular processes of placental stem cells.

Free Research Field

再生医療

Academic Significance and Societal Importance of the Research Achievements

先天性代謝異常症とは、生まれながらに特定の酵素などが欠損し、生体内の物質代謝障害を来たす疾患群である。時に根本的治療として行われる肝移植の侵襲は大きい。我々はこれに替わる新規治療として、ヒト羊膜上皮細胞を用いた細胞移植治療の開発を目指している。本研究で得られた、細胞の多能性制御に関わる分子機構の知見は、細胞調整プロトコルの最適化に繋がり、将来的には先天性代謝異常症の新規治療開発に寄与するものと考える。