A team of researcher has engineered a ‘malaria-in-a-dish’ method that paves the way for better treatments.
Massachusetts Institute of Technology (MIT) researchers have come up with a way to use human liver cells, derived from induced pluripotent stem cells, to screen potential antimalarial drugs and vaccines for their ability to treat the liver stage of malaria infection.
The approach may offer new opportunities for personalized antimalarial drug testing and the development of more effective individually tailored drugs to combat the disease, which causes more than 500,000 deaths worldwide each year.
Author Sangeeta Bhatia said that their 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 by the small available pool of liver cells from human donors and the lack of genetic diversity of these donor cells and to overcome these hurdles, Bhatia and her team reprogrammed human skin cells into induced pluripotent stem cells (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 lab. 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, demonstrating 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 appears in the journal Stem Cell Reports.
Shengyong Ng, Robert E. Schwartz, Sandra March, Ani Galstian, Nil Gural, Jing Shan, Mythili Prabhu, Maria M. Mota, Sangeeta N. Bhatia. Human iPSC-Derived Hepatocyte-like Cells Support Plasmodium Liver-Stage Infection In Vitro, Stem Cell Reports, DOI:10.1016/j.stemcr.2015.01.002