| 研究課題/領域番号 |
20K08327
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| 研究種目 |
基盤研究(C)
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| 配分区分 | 基金 |
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| 応募区分 | 一般 |
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| 審査区分 |
小区分53010:消化器内科学関連
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| 研究機関 | 金沢大学 |
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研究代表者 |
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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| 研究分担者 |
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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| 研究期間 (年度) |
2020-04-01 – 2023-03-31
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| 研究課題ステータス |
交付 (2021年度)
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| 配分額 *注記 |
4,420千円 (直接経費: 3,400千円、間接経費: 1,020千円)
2022年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円)
2021年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
2020年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
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| キーワード | NASH / uncultured ADSCs / ADSC / SVF / Immune therapy / adipose tissue (AT) |
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| 研究開始時の研究の概要 |
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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| 研究実績の概要 |
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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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
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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| 今後の研究の推進方策 |
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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