Liver scaffolds obtained by decellularization: A transplant perspective in liver bioengineering

Abstract

Liver transplantation is the only definitive treatment for many diseases that affect this organ, however, its quantity and viability are reduced. The study of liver scaffolds based on an extracellular matrix is a tissue bioengineering strategy with great application in regenerative medicine. Collectively, recent studies suggest that liver scaffold transplantation may assist in reestablishing hepatic function in preclinical diseased animals, which represents a great potential for application as a treatment for patients with liver disease in the future. This review focuses on useful strategies to promote liver scaffold transplantation and the main open questions about this context. We outline the current knowledge about ex vivo bioengineered liver transplantation, including the surgical techniques, recipient survival time, scaffold preparation before transplantation, and liver disease models. We also highlight the current limitations and future directions regarding in vivo bioengineering techniques.

Effect of Donor Age and Liver Steatosis on Potential of Decellularized Liver Matrices to be used as a Platform for iPSC‐Hepatocyte Culture

“…Both aged livers and low and high steatosis livers were successfully decellularized as all livers had less than 50 ng DNA per mg tissue, which is the standard to establish sufficient decellularization, [15] along with the absence of nuclear content in H&E staining. [16] Histological analysis of the livers showed, consistent with our earlier findings, that aged livers had a denser ECM structure and higher collagen content compared to young livers. We observed the opposite pattern with increasing steatosis levels.…”

Cirrhotic Liver Sustains In Situ Regeneration of Acellular Liver Scaffolds after Transplantation into G-CSF-Treated Animals

“…To resemble functional liver tissue, the transplanted ALS should undergo remodeling to ensure its tissue mechanical properties; therefore, the production of structural ECM proteins is crucial. The liver contains important ECM constituents, such as fibrillar collagens (types I and III) [ 6 , 14 ]. In this study, we observed that cells in the graft produced neo-ECMs (collagen I and reticular fibers) after ALS transplantation.…”

“…While several studies have focused on the recellularization steps before transplantation, ALS transplantation itself has only been partially explored. Although total orthotopic transplantation of ALS would not support the metabolic demands of patients after transplantation, other alternatives can be explored to find new therapeutic tools in the fields of hepatology and regenerative medicine [ 6 ]. For example, ALS could be applied after partial hepatectomy to increase the limit of liver resection [ 6 , 7 ] or the scaffold could be used in partial orthotopic transplantation as a way to create a bioartificial liver that ensures metabolic functions while the patient’s own liver regenerates [ 6 , 8 ].…”

Decellularized porcine vena cava grafts are fully repopulated after orthotopic implantaiton

“…However, achieving proper function of such organs and their lifespan after implantation is still a big challenge. The ideal decellularization method, the source of the cells, their su cient amount, and their optimal delivery into the scaffold are some of the questions that need to be answered before getting closer to the preparation of functioning arti cial organs [13,14].…”

“…The ECM obtained by optimal decellularization preserves bio-inductive properties similar to native tissues. These are the capability of chemotaxis, cell attachment, proliferation, and activation [13,24,25].…”