Developing a human malaria-on-a-chip disease model

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.

This construct allows biochemists and bioengineers to study parasitic interactions in real-time within a microphysiological organ-chip environment, and identify foreseeable off-target effects of the therapeutic compounds.

Image source: Rupar et al. (2023), Scientific Reports.