Study of liver restorative therapy for a murine nonalcoholic steatohepatitis model by the administration of immune-suppressive fractions of autologous adipose tissue-derived stromal cells
Project/Area Number |
20K08327
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53010:Gastroenterology-related
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Research Institution | Kanazawa University |
Principal Investigator |
Nasti Alessandro 金沢大学, 医薬保健学総合研究科, 特任准教授 (20830871)
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Co-Investigator(Kenkyū-buntansha) |
関 晃裕 金沢大学, 医学系, 特任助教 (00733859)
酒井 佳夫 金沢大学, 医学系, 准教授 (80401925)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Granted (Fiscal Year 2021)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | NASH / uncultured ADSCs / ADSC / SVF / Immune therapy / adipose tissue (AT) |
Outline of Research at the Start |
Nonalcoholic steatohepatitis (NASH) is a liver disease with no established treatment. Adipose tissue-derived stromal cells (ADSCs) are able to repair damaged tissues by means of immunomodulation and secretive ability; we will study the repairing of NASH cirrhosis by using NASH mice-derived ADSCs.
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Outline of Annual Research Achievements |
Freshly isolated uncultured adipose tissue-derived stromal cells (u-ADSCs) are useful for regenerative therapy. However, the detailed characteristics and therapeutic efficacy of u-ADSCs obtained from disease-affected hosts are unknown. We compared the properties and therapeutic efficacy of u-ADSCs obtained from wild-type mice and from a mouse model of non-alcoholic steatohepatitis (NASH). Wild-type u-ADSCs and NASH-derived u-ADSCs did not show marked differences as well as their therapeutic effects on NASH-related cirrhosis resulted highly similar, including reductions in inflammation and fibrosis. NASH-derived u-ADSCs, similar to wild-type u-ADSCs, are applicable for reparative and regenerative therapy in mice with NASH.
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Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
In FY2021, non-alcoholic steatohepatitis (NASH) model was established by feeding C57BL/6J mice an atherogenic high-fat diet for 4 (NASH(4w)) or 12 weeks (NASH(12w)), followed by the isolation and characterization of freshly isolated uncultured adipose tissue-derived stromal cells (u-ADSCs). Wild-type u-ADSCs or NASH-derived u-ADSCs were administered to mice with NASH cirrhosis, followed by assessment analyses. Therapeutic effects of NASH(4w)u-ADSCs and NASH(12w)u-ADSCs on mice with NASH-related cirrhosis were similar to the effect of wild-type u-ADSCs. Infiltration of inflammatory cells was reduced, the NAFLD Activity Score (NAS) and fibrosis improved, suggesting that the general properties of u-ADSCs were not significantly affected by NASH.
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Strategy for Future Research Activity |
The u-ADSCs are not solely dependent on MSCs for reparative/regenerative properties, but also other cells contribute to the therapeutic effect on hepatitis. The detailed characterization of u-ADSCs would be intriguing and it can provide insight into the mechanisms underlying specific functions of freshly isolated stromal cells of adipose tissue, particularly in regards of their reparative/restorative effects on injured organs. So, we are planning to further study the u-ADSCs and their derivatives for repair and regenerative therapy, such studies are expected to provide important information regarding specific enriched subpopulations for the development of enhanced cell therapies.
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Report
(2 results)
Research Products
(9 results)
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[Journal Article] Regenerative Therapy for Liver Cirrhosis Based on Intrahepatic Arterial Infusion of Autologous Subcutaneous Adipose Tissue-Derived Regenerative (Stem) Cells: Protocol for a Confirmatory Multicenter Uncontrolled Clinical Trial.2020
Author(s)
Y Sakai, S Fukunishi, M Takamura, O Inoue, S Takashima, S Usui, A Seki, A Nasti, T Ho, K Kawaguchi, A Asai, Y Tsuchiimura, T Muraymoto, T Yamashita, T Yamashita, E Mizukoshi, M Honda, Y Imai, K Yoshama, T Wada, K Harada, K Higuchi, S Kaneko
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Journal Title
JMIR Res Protoc
Volume: 9
Issue: 3
Pages: e17904-e17904
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Adipose tissue-derived stromal cells of steatohepatitis mice are useful for treatment of fibrosis-progressive NASH2020
Author(s)
Akihiro Seki, Yoshio Sakai, Alessandro Nasti, Masatoshi Yamato, Kosuke Ishida, Hiiro Inui, Tuyen Thuy Bich Ho, Kazunori Kawaguchi, Takashi Wada, Shuichi Kaneko
Organizer
AASLD, The Liver Meeting 2020
Related Report
Int'l Joint Research
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[Presentation] Investigator-initiated clinical trial of autologous adipose tissue-derived regenerative (stem) cells therapy for steatohepatitis-related cirrhosis.2020
Author(s)
Yoshio Sakai, Shinya Fukunishi, Masayuki Takamura, Oto Inoue, Soichiro Usui, Shinichiro Takashima, Kazunori Kawaguchi, Akihiro Seki, Akira Asai, Yusuke Tsuchimoto, Alessandro Nasti, Tuyen Thuy Bich Ho, Kazuhide Higuchi, Shuichi Kaneko
Organizer
AASLD, The Liver Meeting 2020
Related Report
Int'l Joint Research
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[Presentation] Adipose tissue derived stromal/stem cells suppress the hepatocyte apoptosis by restoring the Atf6 pathway activity in NASH mice.2020
Author(s)
Masatoshi Yamato, Yoshio Sakai, Hiiro Inui, Akihiro Seki, Alessandro Nasti, Kosuke Ishida, Tuyen Thuy Bich Ho, Kazunori Kawaguchi, Takashi Wada, Shuichi Kaneko
Organizer
AASLD, The Liver Meeting 2020
Related Report
Int'l Joint Research