Abstract
Liver diseases represent a major global health issue, and currently, liver transplantation is the only viable alternative to reduce mortality rates in patients with end-stage liver diseases. However, scarcity of donor organs and risk of recidivism requiring a re-transplantation remain major obstacles. Hence, much hope has turned towards cell-based therapy. Hepatocyte-like cells obtained from embryonic stem cells or adult stem cells bearing multipotent or pluripotent characteristics, as well as cell-based systems, such as organoids, bio-artificial liver devices, bioscaffolds and organ printing are indeed promising. New approaches based on extracellular vesicles are also being investigated as cell substitutes. Extracellular vesicles, through the transfer of bioactive molecules, can modulate liver regeneration and restore hepatic function. This review provides an update on the current state-of-art cell-based and cell-free strategies as alternatives to liver transplantation for patients with end-stage liver diseases.
Highlights
Cirrhosis and hepatocellular carcinoma cause approximately 2 million deaths per year, placing liver disorders among the top 20 most common causes of death worldwide [1]
The mechanisms by which Mesenchymal Stem/Stromal Cells (MSCs) exert their therapeutic effects in models of liver cirrhosis are manifold as largely revealed from preclinical studies, and include activation of autophagy cirrhosis are manifold as largely revealed from preclinical studies, and include activation of and downregulation of transforming growth factor (TGF)-β pathway [45], modulation of the key autophagy and downregulation of transforming growth factor (TGF)-β pathway [45], modulation of enzymes glucosein homeostasis
Human Liver Stem Cells (HLSCs) in patients suffering from liver-based inborn metabolic diseases causing life-threatening neonatal onset of hyperammonemic encephalopathy
Summary
Cirrhosis and hepatocellular carcinoma cause approximately 2 million deaths per year, placing liver disorders among the top 20 most common causes of death worldwide [1]. Inflammatory responses and acute or chronic immune-mediated organ rejection, life-long requirement of immunosuppressive drugs, and incidence of postoperative infections following LT are still unresolved issues Another hassle regards the finding of post-transplantation fibrosis upon evaluation of liver biopsies for histological changes in the long term [15]. Other studies have been performed in non-human primates with genetically-engineered porcine livers and the recipient’s survival almost reached one month [19] This strategy may be considered as a bridge therapy prior to LT in patients for whom no alternative is available. Cell-based and cell-free strategies as well as evolving technologies have shown promises as therapeutic alternatives in patients with end-stage liver diseases, when the liver’s regenerative capacity is impaired and endogenous liver stem cells can no longer cope with chronic insults. The present review aims at summarizing the current state of cell-based and cell-free alternatives to LT for patients with severe liver diseases
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
