Ex vivo revascularization in liver bioengineering. A critical first towards effective transplantation of bioengineered livers

Resumen

To date, liver transplantation is the only available option for patients with terminal liver disease. The problem is the huge lack of organs for transplantation. Therefore, new emerging therapies such as regenerative medicine and organ bioengineering present hope to solve this problem of organ shortage. However, to date no one has been able to generate bioengineered livers that can successfully be transplanted, due to lack of vascular patency in these bioengineered organs, leading to thrombosis in the receptor animal. Thus, the main objective of this thesis was to generate an in vitro assembled vasculature that was stable and functional. In parallel, we have also worked on the creation of an animal model of liver regeneration, in which the revascularized bioengineering grafts can be transplanted. In addition, in collaboration with the research group of Dr. Bart Spee and Dr. Hans Clevers from the University of Utrecht, we tested seeding hepatocytes derived from somatic cells and Lgr5+ adult liver stem cells in liver decellularized ECM, enhancing their hepatic fate and function when seeded in these scaffolds. This may allow the possibility of obtaining a source of hepatic cells which can be expanded into the large numbers required for organ bioengineering, increasing the structural and anatomical complexity of our bioengineering livers. In summary, these results can provide the necessary tools (stable functional vasculature, a novel source of hepatocytes and an animal model for transplantation) to generate bioengineered livers suitable for future translation into the clinic.