new
method to examine potential antimalarial drugs and vaccines possessing
the potential to treat the liver stage of malaria infection has been
engineered by a team of researchers at the Massachusetts Institute of
Technology (MIT) using human liver cells, derived from induced
pluripotent stem cells. Malarial infection caused approximately 500,000
deaths globally every year. This innovative methodology could possibly
present fresh prospects for customized antimalarial drug testing and the
progress of tailor made medication to fight the condition.
Published
in Stem Cell Reports, senior study author Sangeeta Bhatia, MD, PhD, the
director of MIT's Laboratory for Multiscale Regenerative Technologies
and a biomedical engineer at Brigham and Women's Hospital says, "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. This is especially
important given the increasing occurrence of drug-resistant strains of
malaria in the field."
Bites by infected mosquitoes are the reason
behind the spread of malarial infection amongst humans where it finds a
hospitable host for the growth of the parasites initially in the liver
cells followed by the red blood cells. This is the stage where physical
symptoms of the disease come forward. It has been a challenge to
completely wipe out malarial infection as the parasites can stay alive
in the liver and could potentially trigger a relapse by attacking the
bloodstream possibly in the future. One way towards eradication of the
disease would be if there are medicines or vaccines that could target
the liver stage in turn blocking the parasites penetration into the
bloodstream thus preventing a relapse.
Due to the limited access
to the pool of liver cells and the lack of genetic variety of these
human donor cells, the existing processes for demonstrating liver-stage
malaria in a dish are constrained. Hence, it has been quiet difficult to
investigate and develop custom designed drugs for individual patients
as it is hard to ascertain the levels of genetic influences respond to
antimalarial medicines.
Working towards triumphing over these
obstacles, Bhatia and her team reconstructed human skin cells into
induced pluripotent stem cells (iPSCs)--embryonic-like stem cells
skilled at transforming into additional distinctive cell types
significant for investigating a specific infection. iPSCs are,
theoretically, a renewable supplier of liver cells that preserves the
donor's genetic makeup and can be produced from any human donor. These
characteristics apportion a wide-ranging gamut of the human population
to be a symbol of in drug screens and offer the prospect to examine
individualized reactions to antimalarial drugs as well as genetic
influences that control vulnerability to contamination.
The
researchers contaminated iPSC-derived liver cells with numerous malaria
parasites to create prototypical liver-stage malaria in the laboratory.
These cells were susceptible to an antimalarial drug known as
atovaquone; chemical maturation through contact with tiny molecules also
made the cells susceptible to one more antimalarial drug called
primaquine, exhibiting the importance of this methodology for assessing
modern antimalarial drugs.
"Moving forward, we hope to adapt the
iPSC-derived liver cells to scalable, high-throughput culture formats to
support fast, efficient antimalarial drug screens," says lead study
author Shengyong Ng, a postdoctoral researcher in Bhatia's lab. "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."
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