Modeling Malaria with Humanization and Tissue Engineering

The fight against malaria is hampered by the lack of good animal models. The most dangerous malaria parasite, Plasmodium falciparum, has a complex life cycle involving two hosts: mosquitoes and humans. In humans, the parasite has both a liver stage and a red blood cell stage.

Because of its host species specificity, P. falciparum has been challenging to model in vivo, particularly during the liver stage.

Malaria and its life cycle

Humanized Mouse Models of Malaria

One promising approach to modeling the liver stage of malaria parasites is to use mice with humanized livers. An immunodeficient mouse, engineered with susceptibility to a liver injury, can be depopulated of mouse hepatocytes and engrafted with human hepatocytes which repopulate the mouse liver.

The TK-NOG mouse is one such model. These mice, engrafted with human hepatocytes, can be used to model the malaria liver stage. But generation of chimeric liver mice is expensive, difficult, and requires access to specialized mouse strains.

Modeling Malaria with Artificial Livers

Ng et al. report on a new approach to this problem via the use of engineered artificial livers implanted into readily available standard immunodeficient strains, such as nude mice.

The researchers developed porous human ectopic artificial livers (p-HEALs) via tissue engineering and implanted them successfully into the intraperitoneal space of NCr nude mice. In a proof of concept experiment, the team demonstrated that p-HEALs implanted into nude mice could be infected with P. falciparum in vivo.

The authors argue the tissue engineering approach may be more efficient and scalable compared to established chimeric liver models. As a next step, the researchers contemplate a dual humanized mouse with p-HEALs and a human immune system to study host-parasite interactions.

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Ng, S.; March, S.; Galstian, A.; Gural, N.; Stevens, K. R.; Mota, M. M.; Bhatia, S. N. Scientific Reports 2017, 7, 45424.