Advances in Hepatic Tissue Bioengineering with Decellularized Liver Bioscaffold

Abstract

The burden of liver diseases continues to grow worldwide, and liver transplantation is the only option for patients with end-stage liver disease. This procedure is limited by critical issues, including the low availability of donor organs; thus, novel therapeutic strategies are greatly needed. Recently, bioengineering approaches using decellularized liver scaffolds have been proposed as a novel strategy to overcome these challenges. The aim of this systematic literature review was to identify the major advances in the field of bioengineering using decellularized liver scaffolds and to identify obstacles and challenges for clinical application. The main findings of the articles and each contribution for technique optimization were highlighted, including the protocols of perfusion and decellularization, duration, demonstration of quality control—scaffold acellularity, matrix composition, and preservation of growth factors—and tissue functionality after recellularization. In previous years, many advances have been made as this technique has evolved from studies in animal models to human livers. As the field develops and this promising technique has become much more feasible, many challenges remain, including the selection of appropriate cell types for recellularization, route of cell administration, cell-seeding protocol, and scalability that must be standardized prior to clinical application.

Human Liver Stem Cells: A Liver-Derived Mesenchymal Stromal Cell-Like Population With Pro-regenerative Properties

“…To generate a functional liver organ, it is important to recreate the native cell components (hepatocytes, endothelial and epithelial cells), together with the specific hepatic microenvironment (extracellular matrix components), able to give structural and functional support to the new organ. One of the most innovative experimental approaches is represented by technologies for xenotransplantation and tissue engineering that attempt to decellularize and recellularize the residual scaffold with the recipient cells ( Rossi et al, 2019 ). Using rat liver acellular scaffolds (RLAS) as a biological support, HLSCs were able to differentiate into hepatocyte-like cells ( Navarro-Tableros et al, 2015 ; Figure 1 ).…”

Utility of Common Marmoset (Callithrix jacchus) Embryonic Stem Cells in Liver Disease Modeling, Tissue Engineering and Drug Metabolism

“…This approach utilizes the decellularization of livers and recellularization with freshly isolated functional hepatic cells. Decellularization can be achieved by a variety of chemical, mechanical and physical techniques that preserves the original 3D architecture and microvascular network of the liver, including ECM, while removing the entire the cellular content [ 133 , 134 ]. The decellularized liver scaffolds are then repopulated with hepatic cells by perfusion seeding [ 135 ].…”

Bioengineered Mini Human Livers for Transplantation

“…Using the approaches demonstrated in this manuscript, it may one day be possible to generate autologous bioengineered organs for use in human liver transplantation. In addition to progressive advances in decellularization technology, ( 7 ) the past decade has also seen remarkable progress in the differentiation of various liver cell types derived from pluripotent stem cells. ( 3 ) The unique aspect of this study is the generation of a bioengineered rat liver using human liver cells derived entirely from iPSC.…”