Bioengineered functional humanized livers: An emerging supportive modality to bridge the gap of organ transplantation for management of end-stage liver diseases

Abstract

End stage liver diseases (ESLD) represent a major, neglected global public health crisis which requires an urgent action towards finding a proper cure. Orthotropic liver transplantation has been the only definitive treatment modality for ESLD. However, shortage of donor organs, timely unavailability, post-surgery related complications and financial burden on the patients limits the number of patients receiving the transplants. Since last two decades cell-based therapies have revolutionized the field of organ/tissue regeneration. However providing an alternative organ source to address the donor liver shortage still poses potential challenges. The developments made in this direction provide useful futuristic approaches, which could be translated into pre-clinical and clinical settings targeting appropriate applications in specific disease conditions. Earlier studies have demonstrated the applicability of this particular approach to generate functional organ in rodent system by connecting them with portal and hepatic circulatory networks. However, such strategy requires very high level of surgical expertise and also poses the technical and financial questions towards its future applicability. Hence, alternative sites for generating secondary organs are being tested in several types of disease conditions. Among different sites, omentum has been proved to be more appropriate site for implanting several kinds of functional tissue constructs without eliciting much immunological response. Hence, omentum may be considered as better site for transplanting humanized bioengineered ex vivo generated livers, thereby creating a secondary organ at intra-omental site. However, the expertise for generating such bioengineered organs are limited and only very few centres are involved for investigating the potential use of such implants in clinical practice due to gap between the clinical transplant surgeons and basic scientists working on the concept evolution. Herein we discuss the recent advances and challenges to create functional secondary organs through intra-omental transplantation of ex vivo generated bioengineered humanized livers and their further application in the management of ESLD as a supportive bridge for organ transplantation.

Keywords: Bioengineered liver; Omentum; Secondary organ; Transplantation; End stage liver diseases

Core tip: The concept of bioengineering functional humanized neo-organs relies on finding more appropriate immunologically tolerable transplantation site. We have experienced omentum as more appropriate ectopic site with excellent properties of angiogenesis, regeneration, fibrotic reconstruction, and immunological compatibility which together endorse vascularisation, promote tissue healing, and minimize rejection of foreign body. However, regeneration of liver tissue in omentum is still unknown. Despite the amazing breakthroughs in the bioengineered organs, there is much work left to do. The approach described herein harbours enormous potential to overcome the limitations of organ transplantation and may support failing liver through ectopic transplantation as secondary organ.