Integrated treatment strategy for liver I/RI with transcriptional regulation by mesenchymal stem cell

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19897
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: The University of Tokushima
• Principal Investigator: TAKASU Chie 徳島大学, 大学院医歯薬学研究部(医学域), 講師 (70582823)
• Research Collaborator: MORINE Yuji ; SAITO Yu
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: MSC / ADSC / I/RI / Nrf2

Outline of Final Research Achievements

The purpose of this study was to establish the integrated treatment strategy for liver I/RI with Nrf2 activation by adipose-derived stem cells (ADSCs).
We investigated the protective effect of ADRC for liver I/RI through Nrf2 activation, but not be proved. On the other hand, Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, may protect islets viability and function through Nrf2 expression. EGCG group significantly prolonged cell viability after 24hr culture. Nrf2 nuclear translocation was significantly increased in EGCG group compared to control group after 24hr culture. Regarding the clinical setting, we investigated the changes of liver metabolites in hepatectomy (Hx) with I/RI. The principal component analysis revealed remarkably different component profiles between Pre and Post Hx. Valine and Tryptophan significantly increased after Hx.

Free Research Field

医歯薬学、外科系臨床医学、外科学一般

Academic Significance and Societal Importance of the Research Achievements

本研究ではADSCs投与によるNrf2の活性化による肝虚血再灌流傷害時の肝細胞保護作用について検討した。残念ながら、ADSCsによるNrf2を介した肝細胞保護効果は認められなかったが、Nrf2を介した虚血再灌流傷害時の細胞保護効果に関しては膵島移植modelを用いて示すことができた。また肝虚血再灌流傷害時の臨床検体を用いた検討では、抗酸化作用を持ちNrf2経路に関与する代謝物であるValineとTryptophanが肝切除後にupregulateされていることを解明し、肝I/RIの病態解明の一助となる可能性がある。