New technique for studying the life cycle of hepatitis B can help develop cure for the disease -
A new technique for studying the cycle life of hepatitis B could help researchers develop a cure for the disease.
in an article published today in the journal Proceedings of the National Academy of Sciences , Sangeeta Bhatia of MIT and Charles Rice of the Rockefeller University describe using cultures of microfabricated cells to support hepatitis B virus in human liver cells, allowing them to study immune responses and drug treatments
Approximately 400 million people worldwide are infected with the virus hepatitis B (HBV). thereof, a third party will continue to develop life threatening complications, such as cirrhosis and liver cancer.
Although there is a vaccine against HBV effective, only about 50 percent of people in some countries where the disease is endemic are vaccinated. A complete cure of the disease is very rare, once someone has been infected chronically.
"Once a liver cell is infected, the viral genome persists in the nucleus, and can reactivate later," said Bhatia, the John and Dorothy Wilson Professor of Health Sciences and technology and electrical and computer engineering. "So although we have a vaccine, it is important to find a way to address this persistent form of the virus to attempt to identify treatments that could effectively clear."
hepatocytes "niggling"
to develop a treatment for HBV, researchers should be able to study liver cells infected, called hepatocytes, so that they can understand how the virus interacts with them.
But while researchers have been able to infect cultured human hepatocytes with HBV, the limited lifespan of the cells has made it difficult to study the virus, says Bhatia, who is also a Howard Hughes medical Institute investigator and member of MIT's Koch Institute for integrative cancer research and the Institute for medical engineering and science
"This is because the hepatocyte - the main cell in the liver - is unstable, "she said" it is a very finicky cell, and when you isolate it from the liver and try to culture under conventional conditions, it loses.. quickly his liver function directory. "
So the team set out to develop a technique to maintain stable liver cells and work long enough to monitor their response to the virus and antiviral drugs.
they based their approach on a system they had developed to study hepatitis C in which they were able to successfully infect human hepatocytes by the virus and use for comparing the antiviral regimens.
hepatocytes are first modeled on surfaces dotted with small patches of collagen and surrounded by supporting tissue composed of stromal cells, which act as supporting connective tissue and hepatocytes in the exercise of their duties liver.
two complementary systems
to apply the technique to HBV infection, the researchers developed two complementary systems. Using primary hepatocytes obtained from livers donated for transplantation; the second uses stem cells derived from samples of human skin and guided in hepatocyte-like cells, Bhatia said.
When they compared the relative merits of the two systems, they found that primary liver cells had a stronger immune response during infection by the virus progeny of stem cells. However, unlike primary hepatocytes, hepatocyte-like cells provide an unlimited supply of test cells, since researchers can simply grow more than necessary, says Bhatia.
"But having said that, the two systems were able to develop this persistent nuclear form [of HBV], so we think they offer complementary tools," she said.
main authors of this document are Amir Shlomai of Rockefeller University, and graduate student Ramanan Vyas and former postdoc Robert E. Schwartz, both from MIT.
To determine whether cell cultures could be used to test new treatments for the disease, the researchers monitored their response to two existing drugs. They found that the infected cultures responded to the drug in the same manner as liver cells within the body are known to do. This means that the systems could be used to help predict the efficacy of new treatments will be the eradication of the virus from the liver cells, Bhatia said.
Having developed the technique, the researchers now plan to start using it to investigate new treatments for HBV. They also plan to use the model to study natural antiviral response of liver cells in more detail, particularly in trying to understand why cells from different donors were immune responses to disease.
Raymond Chung, vice chief of the gastrointestinal unit at Massachusetts General Hospital, who was not involved in the research, says that despite the availability of effective vaccines, researchers have made some inroads in the elimination of HBV. "While we have excellent suppressive therapies, there is no real cure, largely because we have been handicapped by a lack of robust cell culture models that support HBV infection, "he said.
"The new approach described here provides a way by which we can study more effectively the HBV life cycle, and thereby identify novel agents that block additional steps in this cycle of life" says he. "the use of such an approach could bring us more of a cure for HBV."
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