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Fig. 2 | Journal of Biological Engineering

Fig. 2

From: Bioengineering considerations in liver regenerative medicine

Fig. 2

Liver cell therapy and liver repopulation. a The various types of liver cell therapies. Liver cell therapy utilizes a wide range of cells, from different stages of liver development and different tissue types, to treat acute or chronic liver disease. The liver develops from the liver bud (embryonic liver, E8.5) to form the fetal liver (fetal hepatocytes), neonatal liver, followed by adult liver (hepatocytes, liver progenitor cells, (LPC), biliary tree stem cells (BTSC)). Adult bone marrow (bone marrow-derived mesenchymal cells(BM-MSC), and other bone marrow cells) are also used as a cell source. Human pluripotent stem cells (hPSC) are used for differentiation towards hepatocyte-like cells. In encapsulation, shown below, therapeutic cells are placed within microcapsules to improve cell viability upon transplantation by protecting therapeutic cells. Delivery to the liver is often via the portal vein. b Liver Repopulation. Liver repopulation is an experimental procedure performed in transgenic mice. Activation of transgene in the liver injures or kills endogenous hepatocytes. Because of the regenerative capacity of the liver, the remaining injured cells would normally replicate within the liver to replace, or repopulate any empty areas. Because the endogenous hepatocytes are injured, they are unable to repopulate the liver. At the same time, if healthy hepatocytes are injected into the spleen, they will outcompete the native hepatocytes and will repopulate the liver. This assay can be used to assess the regenerative function of adult hepatocytes. Furthermore, it can be used to create a chimeric mouse with new hepatocytes, which may carry a disease causing gene and be used for disease modeling. Finally, if the host mice are both transgenic and immunodeficient, the animals can be used to bear human hepatocytes within the mouse liver, to create a human in-liver mouse. This can be used for disease modeling or testing hepatotoxicity or drug metabolism of human hepatocytes in mice. These transgenic animals can be used to expand primary hepatocytes, which typically don’t expand in culture

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