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以及对用含RGD肽的点击微珠包裹的永生化肝细胞治疗雄性大鼠肝衰竭的评估。

and evaluation of immortalized hepatocyte encapsulated click-microbeads with RGD peptide for treatment of liver failure in male rats.

作者信息

Win Su Yee, Nittayacharn Pinunta, Ngernmark Jatupoom, Chavalitsarot Mongkol, Thedrattanawong Chitinart, Sa-Ngiamsuntorn Khanit, Hongeng Suradej, Nasongkla Norased

机构信息

Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, Nakhon Pathom, Thailand.

Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.

出版信息

Front Bioeng Biotechnol. 2025 Jul 15;13:1629228. doi: 10.3389/fbioe.2025.1629228. eCollection 2025.

Abstract

Cell encapsulation in biocompatible microbeads offers a promising strategy for cell-based therapy in acute liver failure (ALF). This study evaluates the use of immortalized hepatocyte cells (imHCs) encapsulated in click-arginyl glycyl aspartic acid (click-RGD)-modified alginate microbeads, focusing on their biocompatibility and therapeutic potential. assessments showed that click-RGD microbeads significantly enhanced cell viability on day 4, spatial distribution, and hepatocyte function, evidenced by increased albumin on day 14 and alpha-fetoprotein (AFP) secretion compared to unmodified alginate microbeads. For testing, ALF was induced in Sprague-Dawley male rats using D-galactosamine (D-gal), followed by intraperitoneal administration of imHCs-loaded click-RGD microbeads in the treated group and CMRL medium injection in the control group. Treated rats exhibited faster reductions in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, higher albumin production, and improved liver histology, characterized by reduced necrosis and the absence of inflammation, on day 14 after treatment. No adverse host responses were observed, confirming the biocompatibility of the microbeads. These findings support the potential of click-RGD microbeads as a therapeutic platform for ALF, warranting further studies on long-term implantation, immune response, and co-encapsulation strategies.

摘要

将细胞封装在生物相容性微珠中为急性肝衰竭(ALF)的细胞治疗提供了一种有前景的策略。本研究评估了封装在点击-精氨酰甘氨酰天冬氨酸(click-RGD)修饰的藻酸盐微珠中的永生化肝细胞(imHCs)的应用,重点关注其生物相容性和治疗潜力。评估显示,与未修饰的藻酸盐微珠相比,click-RGD微珠在第4天显著提高了细胞活力、空间分布和肝细胞功能,第14天白蛋白增加和甲胎蛋白(AFP)分泌证明了这一点。为了进行测试,使用D-半乳糖胺(D-gal)在Sprague-Dawley雄性大鼠中诱导ALF,然后在治疗组腹腔注射负载imHCs的click-RGD微珠,在对照组注射CMRL培养基。治疗后的大鼠在治疗后第14天表现出天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)水平更快降低、白蛋白产生增加以及肝脏组织学改善,其特征为坏死减少且无炎症。未观察到不良宿主反应,证实了微珠的生物相容性。这些发现支持click-RGD微珠作为ALF治疗平台的潜力,值得对长期植入、免疫反应和共封装策略进行进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c20/12303912/96caa2630f9d/fbioe-13-1629228-g001.jpg

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