Decellularized liver bioscaffold: a histological and immunohistochemical comparison between normal, fibrotic and hepatocellular carcinoma

Abstract

Aim of the studyIncreasing demand for liver transplantation represents an important health burden. Decellularized liver bioscaffold can be a suitable alternative for whole organ transplantation. However, various pathologies can affect the structure of decellularized scaffolds.This work discusses differences between hepatic fibrosis (HF), hepatocellular carcinoma (HCC) and normal decellularized liver bioscaffolds.Material and methodsMurine models of HF and HCC were created, livers from normal, HF and HCC were decellularized, and evaluation of decellularization was done using morphological, histological and DNA analysis examination. Also, immunohistochemical staining using collagen, laminin, fibronectin and alphafetoprotein was done. Deposition area and intensity of the used immunohistochemical staining in liver capsules and the staining deposition thickness in the blood vessels and hepatic capsule walls were measured for comparison between the three models.ResultsNormal, HF and HCC livers were decellularized efficiently as confirmed by histological and DNA estimation. HCC decellularized samples showed significantly higher collagen, fibronectin and laminin deposition in both capsule and blood vessels, followed by HF decellularized samples, which also showed the highest thickness of laminin deposition in both capsule and blood vessels, then the normal model, which recorded the lowest value. Alphafetoprotein positive cells were absent in normal and HF, with rare cells in HCC.ConclusionsEven pathologic livers, HF and HCC, can be efficiently decellularized, showing normal morphology and architecture. However, HCC and HF showed significantly higher deposition of extracellular matrix proteins: collagen, fibronectin and laminin. The impact of these differences on physiological and immunological functions of the bioscaffold requires recellularization experiments.

Decellularized diseased tissues: current state‐of‐the‐art and future directions

“…It is famed that liver fibrosis is the initiating factor in the occurrence of hepatocellular carcinoma (HCC). Compared with decellularized murine HCC livers that exhibited significantly overexpressed collagen, fibronectin, and laminin deposition in both capsule and blood vessels, decellularized hepatic fibrosis samples showed higher thickness of laminin deposition in both capsule and blood vessels 158 …”

Recreating Tumour Complexity in a Dish: Organoid Models to Study Liver Cancer Cells and their Extracellular Environment

“…This culture system is optimally suited to explore the biological behaviour of cancer cells within natural fibrotic or healthy environments. Recently, Salim et al [130] were able to decellularize and compare healthy, fibrotic and hepatocellular carcinoma rat liver samples on a primarily histological basis. Although the study design was basic and lacking any type of recellularization, it paves the path for more research into the use of decellularized scaffolds as a basis for in vitro PLC research.…”

Emerging trends in modeling human liver disease in vitro

“…In the 3D PEG-collagen hydrogel system, scaffold softening through the treatment with exogenous matrix metalloproteinase (MMP)-1 was shown to enhance HepG2 proliferation, decrease the expression of E-cadherin, and increase the sensitivity to radiation exposure 132 . In addition to synthetic hydrogels, recent studies have examined the efficacy of decellularized rodent, 133,134 porcine, 135,136 and human 137 liver tissues as the basis for 3D culture approaches aimed at better representing the complement of ECM factors present in vivo . In order to directly evaluate the ECM composition and the presence of other key signals within typical liver tumor microenvironments, a broad range of studies have employed a combination of animal models together with the direct assessment of patient samples 138 .…”