In a new report published on Scientific Reports, Michael J. Rupar, and a research team at Hesperos Inc., Florida, U.S., developed a functional, multi-organ, serum-free system to culture P. falciparum—a protozoan that predominantly causes severe and fatal malaria, in order to establish innovative platforms to develop therapeutic drugs.
The platform contained four human organ constructs, including hepatocytes, splenocytes, endothelial cells, and recirculating blood cells, for interactions with the parasitic organism to simulate an infection. The team used two strains of P. falciparum; the 3D7 strain sensitive to chloroquine; a well-established anti-malarial drug, and the W2 strain resistant chloroquine. They maintained functional cells in healthy and diseased conditions for 7 days in the recirculating microfluidic model.
The scientists demonstrated an effective platform for therapeutic development where chloroquine treatment significantly decreased parasitemia in the 3D7 strain-constituent model. They used this setup for therapeutic index determination to evaluate off-target toxicity for anti-malarial treatment in a dose dependent manner. The outcomes can establish a new approach to evaluate anti-malarial therapies in a realistic human model that maintained blood circulation for 7 days.
The parasitic lifecycle occurs in two stages: during a blood meal, sporozoites are released from the saliva of the mosquito, which then travel through peripheral blood circulation to the liver to replicate within hepatocytes. This results in an abundance of merozoites within a few days that are then released from the ruptured hepatocytes to navigate from the liver to the blood stream.
The lifecycle of the merozoites are asexual and erythrocytic, where the parasite develops by infecting blood cells. Rapid asexual replication fueled by the host’s hemoglobin, caused merozoites to enter a ring stage, in 48 hours to then mature into trophozoites and schizonts, which continue to grow and replicate until they burst, releasing more merozoites to repeat the cycle of infection.
2023-07-09 10:48:03
Original from phys.org