Construction of tissue-engineered hepatocyte sheets supplemented with adipose-derived stem cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18063
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Suzushino Seiko 福島県立医科大学, 公私立大学の部局等, 助手 (20816376)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 異所性肝細胞移植 / 間葉系幹細胞 / シート工学

Outline of Final Research Achievements

In this study, we created hepatocyte sheets supplemented with adipose-derived stem cells (ADSCs) and evaluated the effects of ADSCs on hepatocyte function and engraftment into the subcutaneous space.
In vitro, the numbers of viable hepatocytes and dead hepatocytes were significantly higher and lower, respectively, in the hepatocyte-ADSC composite sheets than in hepatocyte-only sheets. In addition, the levels of albumin and the cytokines required for hepatocyte survival were significantly higher in the supernatants of the hepatocyte-ADSC composite sheets than in those of the hepatocyte-only sheets.
The hepatocyte-ADSC composite sheets and hepatocyte-only sheets were transplanted subcutaneously into the recipient mice. 28 days after transplantation, the hepatocyte-ADSC composite sheets were observed to form sheets subcutaneously, but hepatocyte-only sheet was not observed.

Free Research Field

肝細胞移植

Academic Significance and Societal Importance of the Research Achievements

肝細胞移植は、肝臓移植と比較して低侵襲という優位性を認めるが、肝細胞採取による肝細胞障害の問題、門脈内投与による弊害（門脈塞栓や肺塞栓、宿主免疫応答）など、解決すべき命題がある。既報では、組織工学技術を応用した肝細胞シートによる皮下肝細胞移植が報告されているが、多機能な肝臓の一部を補完するのみに留まっている。本研究では、肝臓発生に必須とされる肝細胞と支持細胞との細胞間接着に着目し、比較的低侵襲に採取できるADSCと肝細胞の積層化シートの作製を行い、分離ストレスによる細胞喪失を軽減し、かつ肝細胞を組織として移植することで、効率的な移植技術が確立するものと考える。