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

通过施用自体脂肪组织来源的基质细胞的免疫抑制部分对小鼠非酒精性脂肪性肝炎模型进行肝脏恢复治疗的研究

• 批准号: 20K08327
• 负责人: Nasti Alessandro
• 金额: $ 2.83万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2020
• 资助国家: 日本
• 起止时间: 2020-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-20K08327/
• 关键词: NASH; uncultured ADSCs; ADSC; SVF; Immune therapy; adipose tissue (AT)

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.

新鲜分离的未培养脂肪组织来源的基质细胞(u-ADSCs)可用于再生治疗。然而，从受疾病影响的宿主获得的u-ADSCs的详细特征和治疗效果尚不清楚。我们比较了从野生型小鼠和非酒精性脂肪性肝炎(NASH)小鼠模型中获得的u-ADSCs的特性和治疗效果。野生型u-ADSCs和NASH来源的u-ADSCs没有显著差异，它们对NASH相关肝硬化的治疗效果非常相似，包括炎症和纤维化的减轻。NASH来源的u-ADSCs与野生型u-ADSCs相似，适用于NASH小鼠的修复和再生治疗。

项目成果

Restorative effect of adipose tissue-derived mesenchymal stem cells towards impaired hepatocytes via Notch signaling in a murine model of non-alcoholic steatohepatitis mice

在非酒精性脂肪性肝炎小鼠模型中，脂肪组织来源的间充质干细胞通过 Notch 信号传导对受损肝细胞的恢复作用

• 发表时间: 2021
• 作者: Kosuke Ishida;Yoshio Sakai;Akihiro Seki;Kazunori Kawaguchi;Alessandro Nasti;Hiiro Inui;Takashi Wada;Shuichi Kaneko
• 通讯作者: Shuichi Kaneko

Investigator-initiated clinical trial of autologous adipose tissue-derived regenerative (stem) cells therapy for steatohepatitis-related cirrhosis.

研究人员发起的自体脂肪组织来源的再生（干）细胞治疗脂肪性肝炎相关肝硬化的临床试验。

• 发表时间: 2020
• 作者: 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
• 通讯作者: Shuichi Kaneko

Adipose tissue derived stromal/stem cells suppress the hepatocyte apoptosis by restoring the Atf6 pathway activity in NASH mice.

脂肪组织来源的基质/干细胞通过恢复 NASH 小鼠中的 Atf6 通路活性来抑制肝细胞凋亡。

• 发表时间: 2020
• 作者: Masatoshi Yamato;Yoshio Sakai;Hiiro Inui;Akihiro Seki;Alessandro Nasti;Kosuke Ishida;Tuyen Thuy Bich Ho;Kazunori Kawaguchi;Takashi Wada;Shuichi Kaneko
• 通讯作者: Shuichi Kaneko

Restorative effect of adipose tissue-derived stem cells on impaired hepatocytes through Notch signaling in non-alcoholic steatohepatitis mice

• DOI: 10.1016/j.scr.2021.102425
• 发表时间: 2021-06-10
• 期刊: STEM CELL RESEARCH
• 影响因子: 1.2
• 作者: Ishida，Kosuke;Seki，Akihiro;Sakai，Yoshio
• 通讯作者: Sakai，Yoshio

Jagged1 ON ADIPOSE TISSUE-DERIVED STROMAL / STEM CELLS IS INVOLVED IN THE RESTORATIVE EFFECT ON MURINE NON-ALCOHOLIC STEATOHEPATITIS.

脂肪组织来源的基质/干细胞上的 Jagged1 参与对小鼠非酒精性脂肪性肝炎的恢复作用。

• 发表时间: 2021
• 作者: Kosuke Ishida; Yoshio Sakai; Akihiro Seki; Kazunori Kawaguchi;Alessandro Nasti; Takashi Wada and Shuichi Kaneko
• 通讯作者: Takashi Wada and Shuichi Kaneko