The liver is capable of regenerating itself if a part of it is removed. For years scientists have been looking for a way to exploit this ability and grow liver cells outside the body with the hope that liver tissue, produced artificially, could be used for transplantation.
However, it's been a constant struggle because the cells (called "hepatocytes") lose their function as soon as they are removed from the body.
Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science at MIT, said that it has been a complete "paradox because we know liver cells are capable of growing, but somehow we can't get them to grow".
Yet, a group of researchers, led by Bhatia, have finally managed to find a way to make liver cells function normally in a lab dish and multiply to create new tissue.
The team identified 12 different compounds that allow liver cells to carry on functioning normally even when they aren't inside the body.
The findings, which were published in the June 2 issue of Nature Chemical Biology, could potentially help over 500 million people who suffer from chronic liver diseases such as hepatitis C.
12 compounds hold the key to liver tissue growthIn previous research, Bhatia found that by by intermingling hepatocytes with mouse fibroblast cells the liver cells temporarily maintained normal function.
This new large-scale study used a similar technique so that hepatocytes could grow in layers with the fibroblast cells. The researchers were then able to study over 12,500 different chemicals responsible for liver-cell growth.
David Thomas, an associate researcher working with Todd Golub at the Broad Institute measured the expression levels of 83 different liver enzymes that have proved to be responsible for the most difficult functions to maintain.
The researchers were able to identify 12 compounds that helped maintain those functions, after screening thousands of cells from eight different donors.
In addition, they identified two compounds which worked particularly well among the cells from younger donors, so the team decided to test them in liver cells from induced pluripotent stem cells (iPSCs).
Previous efforts to produce hepatocytes from iPSCs have never resulted in them reaching a fully mature state. However, when the cells were treated with these two compounds it significantly helped them mature.
What are iPSCs?
The team hopes that these compounds could influence other types of cells as well and become the basis for a "universal maturation program".
Plans for future research include implanting the liver cells into mice and seeing whether they can be used as replacement tissues.
The importance of blood vesselsIt's imperative to build blood vessels to keep the tissues alive.
The importance of building blood vessels for new organs was stressed in a previous study by Andrew Putnam, U-M associate professor of biomedical engineering, he said that "it's not just enough to make a piece of tissue that functions like your desired target. If you don't nourish it with blood by vascularizing it, it's only going to be as big as the head of a pen."
His research demonstrated that adult stem cells could solve this problem. A paper on the findings is published online in Tissue Engineering Part A.
Bhatia and colleagues have been working on growing blood vessels to supply the engineered liver tissue with plenty of oxygen and nutrients. Previous research, published in the Proceedings of the National Academy of Sciences, revealed that when preformed cords of endothelial cells are placed into the liver tissue they eventually develop into blood vessels.
Written by Joseph Nordqvist