Analysis of the mechanism underlying liver diseases using human induced pluripotent stem cells

Abstract

Results of recent studies have shown that disease models using human induced pluripotent stem (iPS) cells have recapitulated the pathophysiology of genetic liver diseases, viral hepatitis and hepatic fibrosis. The utilization of human iPS cells as a model of liver diseases has several substantial advantages compared with primary hepatocytes and cancer cell lines, such as the potential for unlimited expansion and similarity of biological characteristics to normal liver cells. In this review, we have focused on modeling liver diseases using human iPS cells and discussed the experimental evidence that supports the utility of such disease models, including that in our recent studies. Genetically modified or patient-derived human iPS cells can mimic congenital liver disease phenotypes. Human iPS-derived hepatic cells can be infected with the hepatitis viruses. The co-culture of human iPS-derived hepatocytes and mesenchyme partially mimics the process of liver fibrosis. Human iPS cell-derived hepatic cells and the co-culture system of such cells will contribute to the progress of studies on the pathophysiology of genetic and non-genetic liver diseases and development of novel therapeutic strategies for treating liver diseases.

The Provocative Roles of Platelets in Liver Disease and Cancer

“…The space of Disse surrounds the sinusoids and constitutes a stem-cell niche that harbors HSCs or liver-resident mesenchymal stem cells that patrol and regulate cellular function within this microenvironment (177)(178)(179)(180)(181). HSCs, antler stem cells, mesenchymal stem cells, and other cells freely migrate within the space of Disse and contribute to regeneration, liver fibrosis, carcinogenesis, and metastasis (177)(178)(179)(180)(181)(182)(183)(184)(185). The complexities of this resident stem-cell space may contribute to the liver becoming an organ of extra-medullary hematopoiesis (Figure 5A) that is also prone to tumor metastasis.…”

Induced Pluripotent Stem Cells for the Treatment of Liver Diseases: Novel Concepts

“…While conducting studies involving the use of patient-derived iPSCs to clarify the unknown pathophysiology of rare genetic liver diseases, there might be confusion owing to unreliable data because of different genetic backgrounds of patients, lack of Yao/Yu/Nyberg Cells Tissues Organs 2022;211:368-384 372 DOI: 10.1159/000508182 a phenotypic marker, various mutation patterns in the disease, and different multipotency of the iPSC cell lines. Therefore, genetically engineered hiPSCs derived from healthy individuals are used to study diseases including liver disease [Kakinuma and Watanabe, 2019]. To determine the functional significance of BA-susceptibility genes identified by genome-wide association studies in biliary development, the CRISPR-Cas9 system was used to created isogenic iPSCs with defined mutations in these genome-wide association studies BA loci (GPC1 and ADD3) from healthy iPSCs.…”

Targeted Integration of Inducible Caspase-9 in Human iPSCs Allows Efficient in vitro Clearance of iPSCs and iPSC-Macrophages

“…Since the development of induced pluripotent stem cells (iPSCs) by Takahashi and Yamanaka in 2006 [1], iPSCs have been proposed for innovative cell-based therapies and as a novel approach for regenerative medicine. Indeed, iPSCs and thereof derived cell types have already been successfully applied as disease modeling and drug discovery platforms [2][3][4]. However, despite immense progress in reprogramming techniques, iPSCs' biology, and differentiation protocols, they are still not available as a standard therapy.…”