2020 Fiscal Year Research-status Report
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 Institution | Kanazawa University |
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Principal Investigator |
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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 – 2024-03-31
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| Keywords | NASH / uncultured ADSCs |
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| Outline of Annual Research Achievements |
NASH is a major cause of chronic liver disease, and effective treatment should be developed. Freshly isolated uncultured adipose tissue-derived stromal cells (u-ADSCs) are advantageous, they have pluripotent and immunomodulatory capabilities. We compared characteristics of u-ADSCs from wild mice and from mice affected by NASH. In the context of surface antigens and gene expression profile features, u-ADSCs from wild mice and u-ADSCs from NASH mice, fed with NASH diet for 4 weeks (NASH-4w) or 12 weeks (NASH-12w), did not show marked differences, except for u-ADSCs isolated from NASH-4w mice which showed a slight increase in frequency of CD11b, CD45 and CD44 surface markers, indicating a possible presence of WBCs, as well as an enhanced cell cycle related gene expression character.
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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
Regarding the research progression in FY2020, all experiments and analyses proceeded steadily. We performed as planned, a full flow cytometry and DNA microarray analyses of uncultured adipose tissue-derived stromal cells (u-ADSCs) and of NASH mice-derived u-ADSCs; regarding the flow cytometry analysis we investigated the expression of the following surface antigens: CD11b, CD73, CD31, CD34, CD90, CD29. CD45, CD105, CD44, Ly6c and Gr-1.
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| Strategy for Future Research Activity |
Following the characterization of uncultured adipose tissue-derived stromal cells (u-ADSCs), we will proceed with the investigation of the effect of wild type u-ADSCs treatment of NASH-cirrhotic mice by evaluating the hepatic inflammatory cells infiltration as well as extent of fibrosis in livers. We are planning to evaluate the hepatic inflammatory cells infiltration using immunohistochemical and flow cytometry analyses, furthermore fibrosis quantification will be performed by staining liver tissue of mice treated with u-ADSCs.
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| Causes of Carryover |
A part of the funds were not used in FY2020 due to the Coronavirus pandemic, funds were not used for the planned travelling expenses and conference fees (national and international conferences). All other expenses in FY2020 proceeded as planned. In FY2021, as well, it is expected the use of funds as planned in the original research plan.
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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
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
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
Int'l Joint Research
