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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Development of an efficient human hepatocyte culture platform for assessing novel therapeutic efficacy against Plasmodium liver parasites

Maher, Steven Patrick 10 July 2014 (has links)
Malaria is a critical and global public health problem, affecting over 200 million people every year, resulting in over 500,000 deaths. A vaccine is not currently available and only one drug, primaquine, is effective against the dormant stages of Plasmodium vivax. Preclinical assessment of novel therapeutic drugs and vaccines is hampered by the lack of an in vitro liver model for P. falciparum and P. vivax. To provide a stable human hepatocyte-based culture platform for parasite development, we engineered a microfluidic bilayer device capable of both simple and complex culture methods, including perfusion and co-culture, to better understand the requirements of both hepatocytes as host cells and parasite liver stage development. As only the mechanical compaction of the device channels was found necessary for stable hepatocyte culture, and only a validated host cell lot was found necessary for improved parasite development rates, we present an efficient and simple Plasmodium liver model capable of supporting P. vivax dormant forms. Device liver platforms were used to generate kill curves of P. vivax and P. falciparum after three days under primaquine drug pressure. Furthermore, an anti-CSP antibody-based inhibition of development assay with P. falciparum successfully demonstrated antibody-specific liver stage inhibition. Ongoing studies aim to identify the minimal unit of the culture system necessary to be multiplexed in a fully functional and efficient drug and vaccine discovery platform.

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