June 3, 2013
Study Brings Artificial Livers One Step Closer To Reality
redOrbit staff & Wire Reports — Your Universe Online
While the liver´s ability to regenerate itself has yet to be successfully harnessed to create artificial liver tissue for use in transplants, a team of researchers believe they are a step closer to overcoming the obstacles keeping this medical breakthrough from becoming a reality.Ordinarily, mature liver cells (also known as hepatocytes) lose their normal function rapidly when they are removed from the body. Now, scientists from the Massachusetts Institute of Technology (MIT), the Broad Institute, Harvard Medical School and the University of Wisconsin have pinpointed a dozen chemical compounds which can help those cells not only continue functionally normally, but also produce new tissue when grown in laboratory dishes.
According to the study authors, liver cells grown in this manner could help researchers develop engineered tissues capable of treating many of the hundreds of millions of people suffering from hepatitis C and other chronic liver conditions. Their findings are detailed in Sunday´s edition of the journal Nature Chemical Biology.
MIT Health Sciences and Technology and Electrical Engineering and Computer Science Professor Sangeeta Bhatia, one of the experts behind the study, had previously developed a method that allowed liver cells to maintain their normal function outside of the body by intermingling them with mouse fibroblast cells.
For this study, Bhatia and her colleagues adapted that system so that the liver cells could grow in layers with those fibroblast cells inside the small depressions of a lab dish. By doing so, the researchers were able to perform large-scale and rapid studies to determine how more than 12,000 different chemicals could affect the growth and function of the liver tissue.
The liver, the investigators said, has approximately 500 different functions across four broad categories — drug detoxification, energy metabolism, protein synthesis and bile production. The researchers measured the expression levels of 83 liver enzymes representative of the most difficult to maintain functions.
“After screening thousands of liver cells from eight different tissue donors, the researchers identified 12 compounds that helped the cells maintain those functions, promoted liver cell division, or both,” the researchers explained. “Two of those compounds seemed to work especially well in cells from younger donors, so the researchers“¦ also tested them in liver cells generated from induced pluripotent stem cells (iPSCs).”
“Scientists have tried to create hepatocytes from iPSCs before, but such cells don't usually reach a fully mature state. However, when treated with those two compounds, the cells matured more completely,” they added. “Bhatia and her team wonder whether these compounds might launch a universal maturation program that could influence other types of cells as well. Other researchers are now testing them in a variety of cell types generated from iPSCs.”
Bhatia´s team plans to conduct future studies in which they plan to embed treated liver cells on polymer tissue scaffolds. They will then implant those cells in mice to test whether or not they could function as replacement liver tissues. Furthermore, the researchers are considering developing the compounds as medications that would allow a patient´s own liver tissue to regenerate.