Development of a novel therapy for liver cirrhosis focusing on humoral factors of cell sheets for liver disease treatment

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08331
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tottori University
• Principal Investigator: ITABA Noriko 鳥取大学, 医学部, 助教 (70457167)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 間葉系幹細胞 / セクレトーム / 肝線維化 / 腎線維化

Outline of Final Research Achievements

This research aims to identify fibrosis-suppressing factors in the humoral factors of a cell sheet for liver disease treatment, which utilizes mesenchymal stem cells (MSCs) and an independently developed drug, IC-2, to enhance the fibrosis-suppressing effect. The goal of this research is to develop a new treatment for liver cirrhosis. The secretome of this sheet underwent a two-step size fractionation process using ultrafiltration and gel filtration chromatography, followed by LC-MS/MS shotgun proteomics analysis to identify candidates for fibrosis-inhibiting factors. We succeeded in narrowing down the proteins. It has become evident that this method can be applied to an in vitro evaluation system for renal fibrosis. Thus, this research has provided crucial knowledge that will not only contribute to the development of treatments for liver cirrhosis but also for renal fibrosis.

Free Research Field

再生医療

Academic Significance and Societal Importance of the Research Achievements

肝硬変は国内の年間死亡者数が約17,000例に達しながら、いまだ有効な治療薬が存在しない。研究者らが開発した、温度応答性培養皿上で間葉系幹細胞(MSCs)に低分子化合物IC-2を添加し作製する「肝疾患治療用細胞シート」は、肝硬変の新規治療法になると期待されるが、外科手術を伴うため侵襲性が高く、すべての患者への適応は困難である。本研究ではこの問題点を打破すべく、肝疾患治療用細胞シートのセクレトームに着目し、肝線維化のみならず腎線維化抑制因子の抽出を進めることができた。本研究成果は、アンメットメディカルニーズとなる肝硬変や腎線維症の新たな治療法開発へと繋がる学術的、社会的に意義深い研究である。