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The Human Liver Hepatocytes and their in vitro Expansion

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Kosheeka
The Human Liver Hepatocytes and their in vitro Expansion

Only liver and hepatocyte transplantation is a successful treatment for late-stage liver disorders, in which the liver has lost its ability to regenerate. There need to be more donors, unfortunately. Drug development needs to consider drug metabolism research in the human liver. Therefore, cells that metabolise medicines similarly to primary human hepatocytes are necessary. The activities of primary human hepatocytes decline in typical two-dimensional culture on an extracellular matrix-coated surface, despite the resected human liver's remarkable capacity for regeneration. In vitro production of functional human hepatocytes is now possible due to recent technological developments in the stem cell research sector.


This approach might provide an abundant source of cells for therapeutic uses. Human hepatocytes and/or their progenitors may also be cultured in vitro in order to better understand how the liver develops and regenerates after injury, to evaluate the risk of drug-induced liver injury, to examine how the hepatitis virus interacts with hepatocytes, to illustrate the mechanisms underlying liver carcinogenesis and toxicological studies, and to aid in the creation of tailored treatments for hepatocellular carcinoma patients.


Advancements in the expansion of hepatocytes

Recent advancements in tissue engineering have provided new possibilities, such as the ability to differentiate pluripotent stem cells into patient-specific human hepatocytes, either from induced pluripotent stem cells or embryonic stem cells. Although the potential for these new stem cell sources to produce hepatocyte-like cells is very promising, there are still some drawbacks. These include the expense and time required to sustain and differentiate cells into hepatocytes and the potential for genetic instability associated with the reprogramming approach, which poses a risk when used for clinical purposes.


Over the past few decades, interest in 3D culture methods has also grown as a way to recreate the in vivo hepatic environment more accurately. By merging three cell types in a single 3D structure—endodermal cells produced from induced pluripotent stem cells, human umbilical vein endothelial cells (HUVECs), and mesenchymal stem cells—researchers were able to develop in vitro some vascularized 3D liver buds that resembled adult liver tissue (MSCs).


Future Prospects

Hepatocyte replacement treatment, a liver transplant alternative for severe liver failure, has made considerable advancements during the past ten years. The use of autologous cell sources is significant because it would eliminate the requirement for systemic immune suppression, which is necessary following liver transplantation. Because previous papers frequently only explain the ideal data, it can be challenging to compare their findings. It is necessary to talk about strategies for standardizing the functional assessment of these cells. For therapeutic purposes, cells must be sufficiently expandable.


Currently, the best approach in terms of cell function and safety is the generation of mature hepatocyte-derived progenitors via treatment with small molecules. To find out if mature hepatocytes taken from patients with severe liver diseases like cirrhosis can be transformed into progenitors with enough functions, more research is needed.

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