Liver cells from Stem Cells can be infected with Malaria and used to test potential drugs

In 2008, the World Health Organization announced a global effort to eradicate malaria, which kills about 800,000 people every year. As part of that goal, scientists are trying to develop new drugs that target the malaria parasite during the stage when it infects the human liver, which is crucial because some strains of malaria can lie dormant in the liver for several years before flaring up.
A new advance by MIT engineers could aid in those efforts: The researchers have discovered a way to grow liver-like cells from induced pluripotent stem cells. These cells can be infected with several strains of the malaria parasite and respond to existing drugs the same way that mature liver cells taken from human donors do.
Such cells offer a plentiful source for testing potential malaria drugs because they can be made from skin cells. New drugs are badly needed, since some forms of the malaria parasite have become resistant to existing treatments, says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology (HST) and Electrical Engineering and Computer Science at MIT.
“Drug resistance is emerging that we are continually chasing. The thinking behind the call to eradication is that we can’t be chasing resistance and distributing bed nets to protect from mosquitoes forever. Ideally, we would rid ourselves of the pathogen entirely,” says Bhatia, who is also a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES).
Until now, malaria researchers have not had many reliable ways to test new drugs in liver tissue. “What’s historically been done is people have tried to make do with the systems that were available,” Bhatia says. Those systems include testing drugs in cancerous liver cells or in mice infected with a rodent-specific version of the malaria parasite. However, cancerous cells divide much more frequently than normal adult liver cells, and are missing some of the genes required for drug metabolism. The mouse model is not ideal because the rodent version of malaria is different from the human one, so drugs that are successful in mice don’t always work in humans.
“This study is a major breakthrough,” says Dyann Wirth, chair of the Department of Immunology and Infectious Diseases at the Harvard School of Public Health, who was not part of the research team. “This technique may prove not only a useful tool for finding drugs that will target the liver stage of the parasite, but it could also contribute to our fundamental understanding of the parasite.”