2021 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 |
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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| Keywords | NASH / uncultured ADSCs / ADSC |
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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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| Causes of Carryover |
Part of the funds were not used in FY2021 due to Coronavirus pandemic (ie.: funds for travelling to conferences not used, etc.). The rest of the expenses were processed as planned. For FY2022, it is expected to use the funds as planned.
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Research Products
(4 results)
