Novel hybrid three-dimensional artificial liver using human induced pluripotent stem cells and a rat decellularized liver scaffold

Abstract

Introduction Liver transplantation is currently the only curative therapy for end-stage liver failure; however, establishment of alternative treatments is required owing to the serious donor organ shortage. Here, we propose a novel model of hybrid three-dimensional artificial livers using both human induced pluripotent stem cells (hiPSCs) and a rat decellularized liver serving as a scaffold. Methods Rat liver harvesting and decellularization were performed as reported in our previous studies. The decellularized liver scaffold was recellularized with hiPSC-derived hepatocyte-like cells (hiPSC-HLCs) through the biliary duct. The recellularized liver graft was continuously perfused with the culture medium using a pump at a flow rate of 0.5 mL/min in a standard CO 2 (5%) cell incubator at 37 °C. Results After 48 h of continuous perfusion culture, the hiPSC-HLCs of the recellularized liver distributed into the parenchymal space. Furthermore, the recellularized liver expressed the albumin ( ALB ) and CYP3A4 genes, and secreted human ALB into the culture medium. Conclusion Novel hybrid artificial livers using hiPSCs and rat decellularized liver scaffolds were successfully generated, which possessed human hepatic functions.

Renal Regeneration: The Role of Extracellular Matrix and Current ECM‐Based Tissue Engineered Strategies

“…[88] These results suggest a regulatory role of endothelial cells, which is an important finding for this field. The iPSCs have also demonstrated their tissue-specific differentiation potential for regenerative strategies when cultured on decellularized matrices of livers, [92] lungs, [93,94] pancreas, [95] and human cardiac ECM. [96] The use of embryonic and/or pluripotent stem cells is of extreme importance for breakthrough advances in cell development and differentiation.…”

Cell Therapy and Bioengineering in Experimental Liver Regenerative Medicine: In Vivo Injury Models and Grafting Strategies

“…Different cell types could be used for repopulating decellularized livers, including primary hepatocytes, iPSCderived hepatocyte-like cells, stem cells, or mesenchymal stromal cells for recellularization of the parenchymal areas, and endothelial progenitor cells or human umbilical vein endothelial cells (HUVEC) for reendothelization [85,[128][129][130][131][132]. However, optimization of the recellularization process is still a challenge when more than one cell type per scaffold is used.…”

Production of Human Pluripotent Stem Cell-Derived Hepatic Cell Lineages and Liver Organoids: Current Status and Potential Applications

“…One of these strategies is the transplantation of hepatocyte sheets onto the surface of mice livers [108]. Additionally, different scaffolds have been used to support hPSC-derived hepatocytes for subsequent transplantation, namely PCL fibers [109] and decellularized livers [110,111]. Besides this, a recent study reported for the first time, to the best of our knowledge, the use of current good manufacturing practice (cGMP)-compliant hepatocytes generated from hPSCs for transplantation [112].…”