Wednesday, 27 February 2013

Pig embryonic stem cells in the treatment of liver failure

Liver failure, whether acute or chronic, is a deadly condition. The liver is unable to perform its normal synthetic and metabolic functions, toxins start to accumulate, the skin turns yellow and the brain slows down. As of now, the only effective treatment is liver transplantation however a cell-line of pig stem cells may one day change this.

Back in the 1990s, Neil Talbot, animal researcher from the USDA Agricultural Research Service (ARS), created a liver pig stem cell line called PICM-19. The line was created from embryonic stem cells (ESCs) taken from an 8 days year old embryo. The line is considered to be "immortal", this means that the cells can replicate indefinetely to infinite numbers and according to Talbot they have the capacity to perform many of the human liver functions.

The PICM-19 cells can develop into both bile duct cells and hepatocytes and have helped Talbot in the past to study the stem cell differentiation process. Hepatocytes play the most crucial role in liver function, being involved in the following processes:
  • Protein synthesis 
  • Protein storage 
  • Transformation of carbohydrates 
  • Synthesis of cholesterol
  • Detoxification
  • Excretion of exogenous and endogenous substances
"The PICM-19 cells are the cells that really do all the metabolic functions of the liver" said Talbot.

Picture of a human liver
Human Liver

According to Talbot, PICM19 derived hepatocytes could theoretically perform the detoxification process from within an artificial liver. The ARS researchers are also experimenting with methods to culture PICM19 hepatocytes without needing the help of "feeder cells". These cells are mouse cells used for growing and culturing embryonic stem cells in vitro. They provide support, holding ESCs in place, nourishing them as well.

Although there is a long way to go before artificial livers become a reality, Talbot says that PICM19 stem cells have other, more immediate applications. For instance, he and his colleagues have succesfully used them to study a wide variety of conditions including:
  • Study malaria
  • Toxoplasmosis
  • Hepatitis viruses

He adds that the cells can be used for liver-cancer research and to examine the changes in the bile duct involved in cystic fibrosis. Talbot believes that PICM-19 cells can be further enhanced via a natural selection-like process, by deliberetaly exposing them to toxins.

"A lot of cells would die, but the survivors would really be tough,"
Finally, he believes that the PICM-19 stem cells can be used to create other types of cells and not only hepatocytes.

"Maybe we want to enable it to make insulin, It will be like a pancreas."
His wish is that one day, transplant lists will get a lot shorter thanks to his PICM-19 line.

Video about Liver acute failure

Recent, Related Posts
- Talbot NC, Caperna TJ, Willard RR, Meekin JH, & Garrett WM (2010). Characterization of two subpopulations of the PICM-19 porcine liver stem cell line for use in cell-based extracorporeal liver assistance devices. The International journal of artificial organs, 33 (6), 348-61 PMID: 20669140 

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