Using humanised mice to understand Plasmodium falciparum growth and development
type: CreativeWork
description: Malaria caused ~250 million cases and ~600,000 deaths in 2022 alone. Although treatments and vaccines are currently available, resistance to frontline drugs and waning efficacy of the available vaccines dampen malaria eradication efforts. Therefore, novel and innovative approaches are needed to better understand the causative Plasmodium parasite and to develop more effective anti-malarial therapies. In-vitro culture has been used to study P. falciparum erythrocytic cycle since 1976, allowing the characterisation of genes and testing of therapies. However, it is known that P. falciparum undergoes genetic changes under continuous culture and there are limitations in the host-parasite interactions that can be explored in-vitro. Humanised mice (HuMice) are immunodeficient mice that can be engrafted with human cells and tissues. They are the only small animal model that can be used to study human restricted P. falciparum in-situ and may provide a unique opportunity to model human malaria infection in-vivo. Herein I describe work where I successfully establish P. falciparum infections in HuMice to characterise parasite changes in different HuMice models in-vivo in the presence or absence of a human immune system model. HuMice were engrafted with either human erythrocytes alone to maintain infection or with human immune cells and human erythrocytes to determine the effect of the human immune system on parasite growth in-vivo. I established two different human immune system HuMice models to characterise changes in parasite growth in-vivo. First, using stem cells to reconstitute the human immune system allowing the development of functional human immune system cells including B and T cells. Secondly, a new approach using PBMC allowing for the reconstitution of differentiated immune cells. The results showed that mice with immune cells had higher parasitaemia than mice engrafted with human erythrocytes alone. The human immune cells in the models were responding to infection, …
abstract: Malaria caused ~250 million cases and ~600,000 deaths in 2022 alone. Although treatments and vaccines are currently available, resistance to frontline drugs and waning efficacy of the available vaccines dampen malaria eradication efforts. Therefore, novel and innovative approaches are needed to better understand the causative Plasmodium parasite and to develop more effective anti-malarial therapies. In-vitro culture has been used to study P. falciparum erythrocytic cycle since 1976, allowing the characterisation of genes and testing of therapies. However, it is known that P. falciparum undergoes genetic changes under continuous culture and there are limitations in the host-parasite interactions that can be explored in-vitro. Humanised mice (HuMice) are immunodeficient mice that can be engrafted with human cells and tissues. They are the only small animal model that can be used to study human restricted P. falciparum in-situ and may provide a unique opportunity to model human malaria infection in-vivo. Herein I describe work where I successfully establish P. falciparum infections in HuMice to characterise parasite changes in different HuMice models in-vivo in the presence or absence of a human immune system model. HuMice were engrafted with either human erythrocytes alone to maintain infection or with human immune cells and human erythrocytes to determine the effect of the human immune system on parasite growth in-vivo. I established two different human immune system HuMice models to characterise changes in parasite growth in-vivo. First, using stem cells to reconstitute the human immune system allowing the development of functional human immune system cells including B and T cells. Secondly, a new approach using PBMC allowing for the reconstitution of differentiated immune cells. The results showed that mice with immune cells had higher parasitaemia than mice engrafted with human erythrocytes alone. The human immune cells in the models were responding to infection, …
author: Wadda, Katty
language: eng
keywords: gene expression, human immune system, humanised mice, in vivo, malaria, P. falciparum
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/92aff509-4eab-4f76-8f82-280f6c351e00/download
license: http://purl.org/NET/rdflicense/allrightsreserved
date published: 2024-09-29
date modified: 2026-07-22T22:24:13Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.117040