Liver engraftment potential of hepatic cells derived from patient-specific induced pluripotent stem cells

Abstract

Human induced pluripotent stem cells (iPSCs) are potential renewable sources of hepatocytes for drug development and cell therapy. Differentiation of human iPSCs into different developmental stages of hepatic cells has been achieved and improved during the last several years. We have recently demonstrated the liver engraftment and regenerative capabilities of human iPSC-derived multistage hepatic cells in vivo. Here we describe the in vitro and in vivo activities of hepatic cells derived from patient specific iPSCs, including multiple lines established from either inherited or acquired liver diseases, and discuss basic and clinical applications of these cells for disease modeling, drug screening and discovery, gene therapy and cell replacement therapy.

Figure 1

In vivo engraftment potential of hepatic cells derived from multiple patient iPSCs. Large area scan images of human albumin (ALB, green) staining in mouse liver transplanted with 2 × 10⁶ hepatic progenitor cells derived from patient iPSC line (iAAT1, iAAT2, iLC1, iLC2, iHCC1 and iHCC9). Liver images were taken using the motorized Nikon Ti-E microscope with an Encoded Motorized XY stage and a function in NIS-Elements to generate these montage images.

Figure 2

Applications of hepatocytes derived from patient-specific iPSCs. Patient-specific iPSCs can be generated from various liver diseases patients and different stages of disease progression. Disease specific iPSC generation and multistage hepatic differentiation technologies can be utilized in liver disease modeling, pathogenesis research, novel drug or molecule discovery, gene therapy and cell therapy.