Formation of Functional Hepatocyte-Like Cells through Direct Conversion and Transplantation into Various Mice Models = Formation of Functional Hepatocyte-Like Cells through Direct Conversion and Transplantation into Various Mice Models

다국어 초록 (Multilingual Abstract)

Aims: The incidence of liver disease is increasing worldwide. Liver transplantation is the only way to treat serious liver diseases. However, demand for transplants is increasing, while supply is very scarce. Therefore, many researchers are studying ways to replace liver transplantation. The most representative of these is cell therapy using ESCs and iPSCs. However, these are not available for clinical use because of the disadvantage that it may form teratoma in the body. Therefore we suggest other method that direct conversion technique produce generation of hepatocyte-like cells from fibroblasts with two liver-specific transcription factors.
Methods: First generation of hepatocyte-like cells (miHeps) were produced by lentivirus infection for continuously expression in host genome during conversion. Second generation of hepatocyte-like cells (R-iHeps) were produced by mRNA transfection. NSG and Albumin-Treck mice were used for in vivo transplantation.
Results: Directly converted hepatocyte-like cells can proliferate, split, store, re-seed, and mature with DMSO. And hepatocyte marker genes and protein expressions, albumin, AFP, etc., were increased in both cells, and albumin secretion in the media was much higher than fibroblasts. Also these cells were transplanted into liver injury model, jo2-treated NSG mice and Albumin-Treck mice, to confirm engraftment in liver. After transplant, miHeps and R-Heps can be detected in the liver under the fluorescence microscope.
Conclusions: Directly converted hepatocyte-like cells can be useful for liver regeneration instead of ESCs and iPSCs-derived hepatocyte-like cells.