Abstract
“Liver medicine” refers to all diagnostic and treatment strategies of diseases and conditions that cause liver failure directly or indirectly. Despite significant advances in the field of liver medicine in recent years, improved tools are needed to efficiently define the pathophysiology of liver diseases and provide effective therapeutic options to patients. Recently, organoid technology has been established as the state-of-the-art cell culture tool for studying human biology in health and disease. In general, organoids are simplified three-dimensional (3D) mini-organ structures that can be grown in a 3D matrix where the structural and functional aspects of real organs are efficiently recapitulated. The generation of organoids is facilitated by exogenous factors that regulate multiple signaling pathways and promote the self-renewal, proliferation, and differentiation of the cells to promote spontaneous self-organization and tissue-specific organogenesis. Newly established protocols suggest that liver-specific organoids can be derived from either pluripotent stem cells or liver-specific stem/progenitor cells. Today, robust and long-term cultures of organoids with the closest physiology to in vivo liver, in terms of cellular composition and function, open a new era in studying and understanding the disease pathology as well as high-throughput drug screening. Of note, these next-generation cell culture systems have immense potential to be further improved by genome editing and bioengineering technologies to foster the development of patient-specific therapeutic options for clinical applications. Here, we will discuss recent advances and challenges in the generation of human liver organoids and highlight emerging concepts for their potential applications in liver medicine.
Highlights
The prevalence of liver diseases is rising, and they account for approximately 2 million deaths per year worldwide (Asrani et al, 2019)
We described a rapid and highly efficient protocol for the production of human hepatic organoids derived from induced pluripotent stem cell (iPSC)
Our study revealed that enrichment of Epithelial Cell Adhesion Molecule (EpCAM)-positive cells resulted in a homogenous population of endodermal cells and licensed the differentiation of functional hepatocytes
Summary
The prevalence of liver diseases is rising, and they account for approximately 2 million deaths per year worldwide (Asrani et al, 2019). Decellularized ferret liver scaffolds were seeded with human fetal progenitor cells containing liver stromal and endothelial cells and incubated in differentiation media for 3 weeks to induce hepatobiliary organoids in an in vitro culture setting This model proved that hepatic and biliary lineage specification and maturation in scaffold was better than for the cells grown in Matrigel, the self-renewal capacity of the organoids and efficiency of this method in recapitulating adult liver functions was comparably low (Figure 2). IPSC-derived EpCAM-positive endodermal cells were isolated and used to generate functional hepatic organoid cultures These organoids exhibited hepatocyte-specific marker gene expression and recapitulated the key metabolic functions of mature hepatocytes, including LDL uptake, albumin secretion, and glycogen storage.
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