Imamura Hiroki, Tomimaru Yoshito, Kobayashi Shogo, Harada Akima, Kita Shunbun, Sasaki Kazuki, Iwagami Yoshifumi, Yamada Daisaku, Noda Takehiro, Takahashi Hidenori, Hokkoku Daiki, Kado Takeshi, Toya Keisuke, Kodama Takahiro, Saito Shigeyoshi, Shimomura Iichiro, Miyagawa Shigeru, Doki Yuichiro, Eguchi Hidetoshi
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, 565-0871, Osaka, Japan.
Department of Cardiovascular Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Sci Rep. 2025 Feb 21;15(1):6334. doi: 10.1038/s41598-025-90805-7.
We investigated the potential of adipose-derived stem cells (ADSCs) in preventing post-hepatectomy liver failure, emphasizing the necessity of direct administration using a scaffold. A fibrin gel scaffold was employed for ADSCs (gelADSC) to assess their therapeutic impact on liver regeneration in both in vitro and in vivo settings. Experiments were conducted on C57BL/6 mice with normal livers and those with chronic hepatitis. We also explored the role of extracellular vesicles (EVs) secreted by ADSCs in conjunction with fibrin gel. GelADSC showed sustained release of hepatocyte growth factor, vascular endothelial growth factor, and stromal cell-derived factor 1 for at least 7 days in vitro. In vivo, gelADSC significantly enhanced postoperative liver regeneration by upregulating the cell cycle and fatty acid oxidation in both normal and chronically hepatitis-affected mice. The therapeutic effects of gelADSC were potentially favorable over those of intravenously administered ADSCs, especially in mice with chronic hepatitis. Increased EV secretion associated with fibrin gel use was significantly linked to enhanced liver regeneration post-surgery through the promotion of fatty acid oxidation. The findings underscore the enhanced therapeutic potential of gelADSC, particularly in the context of chronic hepatitis, possibly compared to intravenous administration.
我们研究了脂肪来源干细胞（ADSCs）在预防肝切除术后肝衰竭方面的潜力，强调了使用支架进行直接给药的必要性。采用纤维蛋白凝胶支架培养ADSCs（凝胶ADSC），以评估其在体外和体内环境下对肝脏再生的治疗作用。对正常肝脏的C57BL/6小鼠和慢性肝炎小鼠进行了实验。我们还探讨了ADSCs分泌的细胞外囊泡（EVs）与纤维蛋白凝胶共同发挥的作用。凝胶ADSC在体外至少7天内持续释放肝细胞生长因子、血管内皮生长因子和基质细胞衍生因子1。在体内，凝胶ADSC通过上调正常和慢性肝炎小鼠的细胞周期和脂肪酸氧化，显著增强了术后肝脏再生。凝胶ADSC的治疗效果可能优于静脉注射ADSCs，尤其是在慢性肝炎小鼠中。与使用纤维蛋白凝胶相关的EV分泌增加与术后通过促进脂肪酸氧化增强肝脏再生显著相关。这些发现强调了凝胶ADSC增强的治疗潜力，特别是在慢性肝炎的背景下，可能优于静脉给药。
