Co-culture Model for Hepatitis B Virus Infection Using iPSC-Derived Liver Progenitor Cells and Liver Sinusoidal Endothelial Cells.

In order to understand the complicated life cycle of hepatitis B virus (HBV), it is necessary to develop a co-culture system for HBV infection using various liver cells. We have already developed culture systems to generate liver progenitor cells (LPCs), hepatocytes, and liver sinusoidal endothelial cells (LSECs) from human induced pluripotent cells (iPSCs). Using those cells, we established a co-culture system to study HBV infection and replication in vitro.

Modulation of hepatitis B virus infection by epidermal growth factor secreted from liver sinusoidal endothelial cells.

Hepatocytes derived from human iPSCs are useful to study hepatitis B virus (HBV) infection, however infection efficiency is rather poor. In order to improve the efficiency of HBV infection to iPSC-derived hepatocytes, we set a co-culture of hepatocytes with liver non-parenchymal cells and found that liver sinusoidal endothelial cells (LSECs) enhanced HBV infection by secreting epidermal growth factor (EGF). While EGF receptor (EGFR) is known as a co-receptor for HBV, we found that EGF enhanced HBV infection at a low dose of EGF, whereas EGF at a high dose suppressed HBV infection.

An In Vitro Human Liver Model by iPSC-Derived Parenchymal and Non-parenchymal Cells.

During liver development, hepatoblasts and liver non-parenchymal cells (NPCs) such as liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs) constitute the liver bud where they proliferate and differentiate. Accordingly, we reasoned that liver NPCs would support the maturation of hepatocytes derived from human induced pluripotent stem cells (hiPSCs), which usually exhibit limited functions. We found that the transforming growth factor β and Rho signaling pathways, respectively, regulated the proliferation and maturation of LSEC and HSC progenitors isolated from mouse fetal livers.

Optimization of a Multi-Product Intra-Supply Chain System with Failure in Rework.

Globalization has created tremendous opportunities, but also made business environment highly competitive and turbulent. To gain competitive advantage, management of present-day transnational firms always seeks options to trim down various transaction and coordination costs, especially in the area of controllable intra-supply chain system. This study investigates a multi-product intra-supply chain system with failure in rework.

Producer-retailer integrated EMQ system with machine breakdown, rework failures, and a discontinuous inventory issuing policy.

This study develops two extended economic manufacturing quantity (EMQ)-based models with a discontinuous product issuing policy, random machine breakdown, and rework failures. Various real conditions in production processes, end-product delivery, and intra-supply chains such as a producer-retailer integrated scheme are examined. The first model incorporates a discontinuous multi-delivery policy into a prior work (Chiu et al.