Cryopreservation of hiPS-derivd hepatic progenitor cells and application to acute liver failure treatment

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08662
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kansai Medical University
• Principal Investigator: SHIROUZU Yasumasa 関西医科大学, 医学部, 講師 (20279186)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ヒトiPS細胞 / 肝細胞

Outline of Final Research Achievements

hiPS cells can be induced into hepatic-lineage cells under the defined culture condition, while the abilities to proliferate have gotten worth and worth during differentiation and the long-term culture of the differentiated hiPS-derived hepatocytes is supposed to be challenging. In the present study, the addition of the cytokine and the low-molecular-weight compounds into the culture medium made the long-term culture more than 20 passages with no serum and no feeder cells possible in the multiple hiPS cell line-derived hepatocytes. Furthermore, they expressed AFP, HNF4a and ALB specific to the hepatic progenitor cells after the long-term culture, and also showed the expression of ASGPR1 and AAT unique to the matured hepatocytes. Moreover, the secretion of ALB to the supernatants was also confirmed.

Free Research Field

肝細胞移植

Academic Significance and Societal Importance of the Research Achievements

肝細胞移植はそのドナー不足と肝細胞のin vitroにおける乏しい増殖能に関連した培養維持の困難さから広く臨床応用されるに至っていない。ヒトiPS細胞は高効率に肝細胞への分化誘導が可能である一方、分化誘導の過程でその増殖能は経時的に低下していき、分化した肝細胞の長期維持培養はヒト由来の肝細胞と同じく困難とされている。本研究ではヒトiPS細胞から分化誘導した肝細胞を長期培養する技術を開発した。さらにその培養維持方法も血清や異種細胞を必要とせず簡便であることから、ヒトへの投与を念頭に置いたさらなる研究の発展が可能で、肝移植を必要とする一部の代謝生肝疾患や急性肝不全の代替医療となりうる期待が持てる。