Cirrhotic hepatocellular carcinoma-based decellularized liver cancer model for local chemoembolization evaluation

Wang，Meijuan1; Gao，Yanan1,2; Liu，Xiaoya1; Li，Zhihua1; Xiao，Jingyu1; Gao，Xu1; Gibson，Matthew I.2,3,4; Guo，Qiongyu1

2024

10.1016/j.actbio.2024.01.020

Acta Biomaterialia   影响因子和分区

1742-7061

1878-7568

Transarterial chemoembolization (TACE) is a common treatment for unresectable intermediate stage hepatocellular carcinoma (HCC) and involves the combination of chemotherapy agents and embolic materials to target and block the blood supply to the tumor, leading to localized treatment. However, the selection of clinical chemoembolization agents remains limited, and the effectiveness of various agents is still under investigation. Meanwhile, replicating the complex vasculature and extracellular matrix (ECM) circumstances of HCC in in vitro models for evaluating embolic agents proves to be challenging. Herein, we developed a decellularized cancerous liver model with translucent appearance, a complicated hepatic vascular system and tissue-specific ECM for the evaluation of embolic agents. Inkpad oil and microparticles were used to illustrate different systems of vascular structures between healthy and HCC rats’ livers. Quantitative analysis with AngioTool revealed significant differences in vessel density and lacunarity between the two groups. Proteomics showed higher secretion of collagens in the HCC rat liver models than in healthy livers. Utilizing this in vitro model, we investigated the impact of tumor-specific vascular structure and ECM composition on chemoembolization performance, the two key factors inaccessible by currently available drug release testing platforms. Our findings revealed that the presence of an aberrant vascular system and the distorted ECM within the model led to drug retention. This preclinical model holds great promise as a valuable tool for evaluating embolic agents and studying their performance in the tumor microenvironment. Statement of significance: Transarterial chemoembolization (TACE), which employs drug-eluting embolic agents to obstruct the tumor-feeding vessels while locally releasing chemotherapeutic drugs into the tumor, has become the first-line treatment of unresectable liver cancer over past two decades. Nevertheless, the advancement of effective drug-eluting embolic agents has been retarded due to the lack of appropriate in vitro models for assessing the local embolization and chemotherapy performances in TACE. Here we developed a cirrhotic hepatocellular carcinoma-based decellularized liver cancer model, which preserves the aberrant vasculatures and tumor-specific extracellular matrix of liver cancer, for TACE evaluation. This model incorporates a blood flow simulation component to assess the dynamics of drug release behaviors of chemoembolic agents within tumor-mimicking conditions, more accurately replicating the in vivo environment for the locoregional assessments as compared to conventional in vitro models.

Chemoembolization Decellularized cancerous liver model Extracellular matrix Hepatocellular carcinoma Vasculature

SCI ; EI

英语

第一 ; 通讯

2-s2.0-85184014367

Scopus

1.Department of Biomedical Engineering,Shenzhen Key Laboratory of Smart Healthcare Engineering,Guangdong Provincial Key Laboratory of Advanced Biomaterials,Southern University of Science and Technology,Shenzhen,Guangdong,518055,China
2.Department of Chemistry and Division of Biomedical Sciences,Warwick Medical School,University of Warwick,Coventry,Gibbet Hill Road,CV4 7AL,United Kingdom
3.Department of Chemistry,University of Manchester,Manchester,Oxford Road,M13 9PL,United Kingdom
4.Manchester Institute of Biotechnology,University of Manchester,Manchester,131 Princess St,M1 7DN,United Kingdom

Wang，Meijuan,Gao，Yanan,Liu，Xiaoya,et al. Cirrhotic hepatocellular carcinoma-based decellularized liver cancer model for local chemoembolization evaluation[J]. Acta Biomaterialia,2024,176:144-155.

Wang，Meijuan.,Gao，Yanan.,Liu，Xiaoya.,Li，Zhihua.,Xiao，Jingyu.,...&Guo，Qiongyu.(2024).Cirrhotic hepatocellular carcinoma-based decellularized liver cancer model for local chemoembolization evaluation.Acta Biomaterialia,176,144-155.

Wang，Meijuan,et al."Cirrhotic hepatocellular carcinoma-based decellularized liver cancer model for local chemoembolization evaluation".Acta Biomaterialia 176(2024):144-155.