Massachusetts Institute of Technology (MIT) researchers have discovered a new way to model malaria using stem cells in a petri dish, which will allow them to test potential antimalarial drugs and vaccines.
Malaria is caused by parasites that spread between humans through the bites of infected mosquitoes. It affects 250 million people and causes approximately one million deaths each year. People with malaria suffer from fever, chills, flu-like illness and, when left untreated, more severe complications and death.
In humans, the parasites first invade liver cells, where they multiply, and then they are released into the blood stream, where they infect red blood cells, causing the physical symptoms of the disease. One major challenge to eradicating malaria is that the parasites can persist in the liver and cause relapses by invading the bloodstream weeks or even years later. Drugs or vaccines that target the liver stage could prevent the initial release of the blood infection or perhaps even eradicate the dormant parasite pool and prevent relapse.
The team at MIT created their disease model using human liver cells derived from induced pluripotent stem cells, also called iPS cells. These cells were created by reprogramming human skin cells in the lab to behave like embryonic stem cells, with the capacity to become any cell type in the body. They were then directed to specialize into liver cells.
To date, methods for studying liver-stage malaria in a dish have been limited by a small pool of donors and a resulting lack of genetic diversity in samples. These challenges have made it difficult to determine how genetics influence responses to antimalarial drugs and to establish a method to explore the development of personalized drugs for individual patients.
The use of iPS cells (which retain a donor’s genetic makeup) in disease modeling allows for screening drugs across a large and diverse group, representative of a wide range of people. This allows researchers to test how different people might respond to a particular antimalarial drug, as well as genetic factors that determine susceptibility to infection.