Humanized Mice As Preclinical Models For Liver Stage Malaria Infection

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Humanized Mice As Preclinical Models For Liver Stage Malaria Infection

Malaria continues to affect 250 million people around the world and causes more than half a million deaths each year. And especially given the global heath community’s current goal of malaria eradication (as opposed to the past approach of merely keeping the parasite at bay), it is increasingly important for researchers to have access to a readily available, scalable in vivo models with humanized livers for use in preclinical settings.

The malaria liver stage occurs early in the parasite’s life cycle – soon after infection of the human host – and during this stage, the infection is an attractive target for the development of antimalarial drugs and/or vaccines.  Humanized mice with chimeric tissues have traditionally been used for malaria research during the liver stage, but they are limited do to the fact that they have variable engraftment rates, lengthy engraftment time, are costly and difficult to breed. However, a new paper by Ng, et al published in Scientific Reports discusses the benefits of a new and improved humanized mouse model that is created by implanting PEG cryogel-based porous human ectopic artificial livers (p-HEALs) into the murine specimens.

According to their paper “Towards a Humanized Mouse Model of Liver Stage Malaria Using Ectopic Artificial Livers”, Ng, et al were able to effectively infect these p-HEALs with Plasmodium sporozoites in vivo without host liver injury.  Although this model certainly needs further optimization, including but not limited to, vascularization, high engraftment of human pladmodium species and the ability to combine with a humanized immune system, it demonstrates that it is feasible to create a “humanized mouse model of liver stage human malaria using tissue engineering rather than genetic approaches”. Furthermore, this gives hope to researchers that a new, more efficient and highly scalable method by which to create preclinical models of liver stage human malaria is on the horizon.

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