A Massachusetts Institute of Technology (MIT) research team has engineered a way to use human liver cells, derived from induced pluripotent stem cells (iPSCs), to screen potential antimalarial drugs and vaccines for their ability to treat the liver stage of malaria infection. This novel approach may offer new opportunities for personalized antimalarial drug testing and the development of more effective individually tailored drugs to combat the disease, which leads to more than 500,000 deaths worldwide each year.
Author Sangeeta Bhatia said, "Our platform can be used for testing candidate drugs that act against the parasite in the early liver stages, before it causes disease in the blood and spreads back to the mosquito vector and this is especially important given the increasing occurrence of drug-resistant strains of malaria in the field."
However, current methods for modeling liver-stage malaria in a dish are limited due to the small available pool of liver cells from human donors and the lack of genetic diversity of these donor cells. To overcome these hurdles, Bhatia and her research team reprogrammed human skin cells into iPSCs, embryonic-like stem cells capable of turning into other specific cell types relevant for studying a particular disease.
The researchers infected iPSC-derived liver cells with various malaria parasites to model liver-stage malaria in the laboratory. They found that these cells were sensitive to an antimalarial drug called atovaquone. Chemical maturation through exposure to small molecules also made the cells sensitive to another antimalarial drug called primaquine. Thus, they demonstrated the value of this approach for testing new antimalarial drugs.
Lead author Shengyong Ng said, "The use of iPSC-derived liver cells to model liver-stage malaria in a dish opens the door to study the influence of host genetics on antimalarial drug efficacy and lays the foundation for their use in antimalarial drug discovery."
The study is published in the journal of the International Society for Stem Cell Research.