Toward Transplantation of Liver Organoids: From Biology and Ethics to Cost-effective Therapy

Abstract

Liver disease is a common cause of morbidity and mortality, and many patients would benefit from liver transplantation. However, because of a shortage of suitable donor livers, even of those patients who are placed on the donor liver waiting list, many do not survive the waiting time for transplantation. Therefore, alternative treatments for end-stage liver disease need to be explored. Recent advances in organoid technology might serve as a solution to overcome the donor liver shortage in the future. In this overview, we highlight the potential of organoid technology for cell therapy and tissue engineering approaches. Both organoid-based approaches could be used as treatment for end-stage liver disease patients. Additionally, organoid-based cell therapy can also be used to repair liver grafts ex vivo to increase the supply of transplantable liver tissue. The potential of both approaches to become clinically available is carefully assessed, including their clinical, ethical, and economic implications. We provide insight into what aspects should be considered further to allow alternatives to donor liver transplantation to be successfully clinically implemented.

Advancing Organoid Engineering for Tissue Regeneration and Biofunctional Reconstruction

“…However, hepatocyte proliferation and liver regeneration diminish with liver injury. Due to the lack of effective treatments for liver failure, new regenerative strategies are needed that stimulate and support endogenous repair mechanisms to rejuvenate or replace the original liver [ 37 ]. Engineered organoid technology has significant potential to replace the original damaged liver and restore normal physiology and function [ 199 ].…”

“…Engineered organoid technology has significant potential to replace the original damaged liver and restore normal physiology and function [ 199 ]. Organoid-based regenerative medicine therapies can also be used for the ex vivo repair of liver grafts to increase the supply of transplantable liver tissue [ 37 ].…”

“…The cost of organoid-based cell therapy (CT) is estimated to be between €276,000 and €801,000 (since CT requires a smaller number of cells, which significantly reduces the cost of tissue production; however, not all patients meet the indications for CT). Alarmingly, the cost of organoid-based tissue engineering is projected to be €6.858 million to €7.041 million [ 37 ]. Preliminary cost estimates suggest high costs associated with organizing production [ 269 ].…”

“…Applying bioengineering principles to organoids can enhance reproducibility, ensure experimental controllability, improve culture efficiency, optimize the tissue structure and physiological function of organoids, and pave the way for the clinical translation of organoids. Engineered organoids can be used to treat injuries caused by most factors, including various disease types affecting the brain [ 33 ], skin [ 34 ], bone and cartilage [ 35 , 36 ], liver [ 37 ], and endocrine glands [ 38 ]. Moreover, organoid engineering approaches have been successfully applied to organoid construction to achieve tissue repair and biofunction reconstruction.…”

Cholangiocyte Organoids: The New Frontier in Regenerative Medicine for the Study and Treatment of Cholangiopathies

“…Notably, organoids adapt well to large-scale expansion, enabling the generation of autonomous mini-liver structures with a vascular network, addressing many challenges in regenerative medicine [ 120 ]. The presence of hepatic organoids fuels the prospect of implementing autologous organ transplants, where healthy patient liver tissues can be expanded and subsequently transplanted, thereby reducing the risk of adverse immune reactions [ 121 ].…”