Present and Future Perspectives of Using Human-Induced Pluripotent Stem Cells and Organoid Against Liver Failure

Abstract

Organ failure manifests severe symptoms affecting the whole body that may cause death. However, the number of organ donors is not enough for patients requiring transplantation worldwide. Illegal transplantation is also sometimes conducted. To help address this concern, primary hepatocytes are clinically transplanted in the liver. However, donor shortage and host rejection via instant blood-mediated inflammatory reactions are worrisome. Induced pluripotent stem cell-derived hepatocyte-like cells have been developed as an alternative treatment. Recently, organoid technology has been developed to investigate the pathology and mechanism of organoids in cultures. Organoids can be transplanted with vascularization and connected to host blood vessels, and functionally mature better in vivo than in vitro. Hepatic organoids improve pathology in liver disease models. In this review, we introduce induced pluripotent stem cell- and organoid-based therapies against liver diseases considering present and future perspectives.

Regenerative hepatology: In the quest for a modern prometheus?

“…HT was originally introduced as a potential alternative to OLT and it has been proven beneficial in selected patients with inborn metabolic errors or ALF 8,13,14 . Donor livers unsuitable for transplantation, surgically resected hepatic tissue or even deceased donor organs with prolonged warm ischemia time, have so far represented common sources of primary hepatocytes.…”

“…In addition, the microvasculature and the biliary network of the host organ is preserved thus potentially favouring organ recovery even in cases of extensive liver damage as in most cases of ALF 18 . However, low cell viability and proliferation rates following cryopreservation, instant blood-mediated inflammatory reaction (IBMIR) and limited cell engraftment 13,19 are the main reasons preventing a more widespread use of HT. Therefore, although there have been a significant number of studies presenting HT in hepatic inborn errors of metabolism [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] and ALF [35][36][37][38][39] , the applicability and effectiveness of this approach are still debated.…”

Engineering the Vasculature of Stem-Cell-Derived Liver Organoids

“…In one study, the hospital survival rate of patients with acute-on-chronic liver failure (ALF) increased from 16.7% to 62.2% after transplantation [2]. However, the supply of livers for transplantation cannot meet the demand as the number of patients on waiting lists for transplantable livers increases continually [3].…”

Downregulation of Augmenter of Liver Regeneration Impairs the Therapeutic Efficacy of Liver Epithelial Progenitor Cells Against Acute Liver Injury by Enhancing Mitochondrial Fission

“…Acute liver injury (ALI) is a life-threatening state associated with high mortality due to severe and rapid loss of liver function. [1][2][3] Currently, orthotopic liver transplantation (OLT) is considered the most effective therapeutic strategy for end-stage liver diseases including ALI. However, application of OLT is significantly limited by a shortage of available donor organs.…”