去细胞化
肝细胞
球体
细胞外基质
纤维化
化学
细胞生物学
自愈水凝胶
肝星状细胞
肝功能
病理
医学
生物
内科学
生物化学
体外
有机化学
作者
Xin‐Yu Chou,Kian-Kai Cheng,Wei‐Rong Yin,Tzong‐Jih Cheng,Richie L. C. Chen,Shan‐hui Hsu,Yung‐Te Hou
标识
DOI:10.1002/mabi.202300411
摘要
Abstract Liver fibrosis occurs in many chronic liver diseases, while severe fibrosis can lead to liver failure. A chitosan‐phenol based self‐healing hydrogel (CP) integrated with decellularized liver matrix (DLM) is proposed in this study as a 3D gel matrix to carry hepatocytes for possible therapy of liver fibrosis. To mimic the physiological liver microenvironment, DLM is extracted from pigs and mixed with CP hydrogel to generate DLM‐CP self‐healing hydrogel. Hepatocyte spheroids coated with endothelial cells (ECs) are fabricated using a customized method and embedded in the hydrogel. Hepatocytes injured by exposure to CCl 4 ‐containing medium are used as the in vitro toxin‐mediated liver fibrosis model, where the EC‐covered hepatocyte spheroids embedded in the hydrogel are co‐cultured with the injured hepatocytes. The urea synthesis of the injured hepatocytes reaches 91% of the normal level after 7 days of co‐culture, indicating that the hepatic function of injured hepatocytes is rescued by the hybrid spheroid‐laden DLM‐CP hydrogel. Moreover, the relative lactate dehydrogenase activity of the injured hepatocytes is decreased 49% by the hybrid spheroid‐laden DLM‐CP hydrogel after 7 days of co‐culture, suggesting reduced damage in the injured hepatocytes. The combination of hepatocyte/EC hybrid spheroids and DLM‐CP hydrogel presents a promising therapeutic strategy for hepatic fibrosis.
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