Fabrication of a decellularized liver matrix–based hepatic patch for the repair of CCl4-induced liver injury

IF 3.2 3区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Biotechnology Journal Pub Date : 2024-06-12 DOI:10.1002/biot.202300570
Ting-Yi Wu, Yi-Cheng Hsieh, Wei-Rong Yin, Kai-Yi Cheng, Yung-Te Hou
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Abstract

This article primarily introduces a new treatment for liver fibrosis/cirrhosis. We developed a hepatic patch by combining decellularized liver matrix (DLM) with the hepatocyte growth factor (HGF)/heparin–complex and evaluated its restorative efficacy. In vitro prophylactic results, the HGF/heparin–DLM patches effectively mitigated CCl4-induced hepatocyte toxicity and restored the cytotoxicity levels to the baseline levels by day 5. Furthermore, these patches restored albumin synthesis of injured hepatocytes to more than 70% of the normal levels within 5 days. In vitro therapeutic results, the urea synthesis of the injured hepatocytes reached 91% of the normal levels after 10 days of culture, indicating successful restoration of hepatic function by the HGF/heparin–DLM patches in both prophylactic and therapeutic models. In vivo results, HGF/heparin–DLM patches attached to the liver and gut exhibited a significant decrease in collagen content (4.44 times and 2.77 times, respectively) and an increase in glycogen content (1.19 times and 1.12 times, respectively) compared to the fibrosis group after 1 week, separately. In summary, liver function was restored and inflammation was inhibited through the combined effects of DLM and the HGF/heparin–complex in fibrotic liver. The newly designed hepatic patch holds promise for both in vitro and in vivo regeneration therapy and preventive health care for liver tissue engineering.

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制作基于脱细胞肝基质的肝补片,用于修复 CCl4 引起的肝损伤。
本文主要介绍一种治疗肝纤维化/肝硬化的新方法。我们开发了一种将脱细胞肝基质(DLM)与肝细胞生长因子(HGF)/肝素复合物相结合的肝脏贴片,并评估了其修复功效。体外预防结果显示,肝细胞生长因子/肝素-DLM贴片有效减轻了CCl4诱导的肝细胞毒性,并在第5天将细胞毒性水平恢复到基线水平。此外,这些贴片还能在 5 天内将受损肝细胞的白蛋白合成量恢复到正常水平的 70% 以上。在体外治疗结果中,受伤肝细胞的尿素合成在培养 10 天后达到正常水平的 91%,这表明 HGF/肝素-DLM 贴片在预防和治疗模型中都成功地恢复了肝功能。体内结果显示,与纤维化组相比,贴在肝脏和肠道上的 HGF/ 肝素-DLM 贴片在 1 周后胶原含量显著下降(分别为 4.44 倍和 2.77 倍),糖原含量显著增加(分别为 1.19 倍和 1.12 倍)。总之,在 DLM 和 HGF/肝素复合物的共同作用下,纤维化肝脏的肝功能得到了恢复,炎症也得到了抑制。新设计的肝脏补片有望用于肝脏组织工程的体外和体内再生治疗和预防保健。
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来源期刊
Biotechnology Journal
Biotechnology Journal Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
8.90
自引率
2.10%
发文量
123
审稿时长
1.5 months
期刊介绍: Biotechnology Journal (2019 Journal Citation Reports: 3.543) is fully comprehensive in its scope and publishes strictly peer-reviewed papers covering novel aspects and methods in all areas of biotechnology. Some issues are devoted to a special topic, providing the latest information on the most crucial areas of research and technological advances. In addition to these special issues, the journal welcomes unsolicited submissions for primary research articles, such as Research Articles, Rapid Communications and Biotech Methods. BTJ also welcomes proposals of Review Articles - please send in a brief outline of the article and the senior author''s CV to the editorial office. BTJ promotes a special emphasis on: Systems Biotechnology Synthetic Biology and Metabolic Engineering Nanobiotechnology and Biomaterials Tissue engineering, Regenerative Medicine and Stem cells Gene Editing, Gene therapy and Immunotherapy Omics technologies Industrial Biotechnology, Biopharmaceuticals and Biocatalysis Bioprocess engineering and Downstream processing Plant Biotechnology Biosafety, Biotech Ethics, Science Communication Methods and Advances.
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