The new method for the liver failure using the hybrid transplantation of the liver and Muse cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10504
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Tohoku University
• Principal Investigator: Shigehito Miyagi 東北大学, 大学病院, 准教授 (00420042)
• Co-Investigator(Kenkyū-buntansha): 後藤 昌史 東北大学, 医学系研究科, 教授 (50400453) ; 戸子台 和哲 東北大学, 大学病院, 助教 (50581641) ; 原 康之 東北大学, 医学系研究科, 非常勤講師 (50636008) ; 中西 渉 東北大学, 大学病院, 助教 (50636024) ; 宮澤 恒持 東北大学, 医学系研究科, 非常勤講師 (80757237)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: Muse細胞 / 心停止ドナーグラフト / 過小グラフト / 酸素化灌流 / 類洞微小循環

Outline of Final Research Achievements

The treatment for the sinusoidal microcirculatory injury (SMI) induced by excessive shear stress to liver sinusoidal endothelial cells (LSECs) is necessary for the regeneration. Multilineage-differentiating Stress Enduring (Muse) cells selectively home to the injured organ and repair by spontaneously differentiation. We hypothesized that intravenous administration of Muse cells might improve SMI the sinusoid. Then we evaluated the protective effects of Muse cells using an extra-small partial liver transplantation model in rats. The analysis of liver sinusoidal images, indocyanine green test, immunohistochemical stain of LSECs revealed that sinusoidal continuity, volume and surface area were protected significantly by administrated Muse cells. Furthermore, Ki-67 positive ratio of hepatocyte is higher in Muse group. The combination of cell transplantation using Muse cells and organ transplantation of small-for-size grafts is effective as a treatment for end-stage of liver disease.

Free Research Field

肝再生、肝移植

Academic Significance and Societal Importance of the Research Achievements

肝不全治療における新たな手法、臓器移植と細胞移植のハイブリッド移植という新たな治療の臨床応用へのきっかけを作るこ事ができた。Muse細胞のすぐれた組織修復能力と抗炎症効果が確認でき、今後の再生医療におけるきっかけとなった。過小肝グラフト移植などにおける類洞内皮障害や門脈圧亢進症状（SFSS）の改善というレベルでの効果は、Museの組織修復能力は有効だと確認できた。今後の研究継続が必要である。