In Vitro expansion of Human Liver Cells from Stem cells now a success?

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Making history in Stem Cell Research, scientists from the Stem Cell Institute and Department of Physiology, university of Cambridge, have developped a method to expand human hepatocytes in vitro. Even though human liver cells shw enormus replication potential there was no any established method to maintain the hepatocyte replication while keeping functioning in vitro.

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In this resarch scientists describe conditions allowing long-term expansion of adult bile duct-derived bipotent progenitor cells from human liver. They have been able to do this by a combination of chemically defined media and 3D suspension culture which allows for the formation of organoids from ductal cells (a cell type in the liver), which essentially takes advantage of the intrinsic ability for the cells to cluster and differentiate together as they would naturally in vivo. The cells that are maintained in culture are also able to form hepatocytes (the cells responsible for detoxification processes) which can be transplanted into a mouse and perform normal function.

 

And also they also show that these artificially expanded cells are genatically stable over time in culture through genomic studies. Apparantly if these are genatically unstable over the time in culture it may complicate their use for regenerative medicine purposes.

 

Scientists note that these cells can be used to study liver diseases like A1AT and Alagile Syndrome, where their organoids show similar phenotypes that are characteristic of these diseases.

 

 

Additionally, they show that these cells are genetically stable over time in culture through whole genome sequencing. Apparently, other groups have reported genetic instability during similar differentiation experiments. As they mention, genetic changes that accrue over time in culture “may complicate their use for regenerative medicine purposes.”

They note that these cells can be used to study liver diseases like A1AT and Alagile Syndrome (I’m not familiar with these), where their organoids show similar phenotypes that are characteristic of these diseases. Using genetic engineering strategies like the CRISPR/Cas9 system, you could in theory take a liver biopsy from an A1AT patient, genetically correct the mutation responsible for the disease, expand the cells in vitro, and transplant them back into the patient. This is a strategy that is essential to the idea behind regenerative medicine and is applicable to a wide range of genetic diseases.

In summary, “long-term expansion of primary adult liver stem cells opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine, and gene therapy”

 

And these in vitro expanded cels will be of great help specially in toxicology studies where new drugs can be screened to check posible effects on liver cells.

The Complete publication is available in this link 

 

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