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Preprints

Persistence of Plasmodium cynomolgi hypnozoites in cynomolgus monkey iPS-derived hepatocytes

Pellisson M, Zeeman A, Doll T, Kirchhofer-Allan L, Schuierer S, Roma G, Flannery EL, Mikolajczak SA, Kocken CHM, Maeser P, Rottmann M, Mueller M.
Preprint from
bioRxiv
18 November 2021
PPR
PPR421675
Abstract
Plasmodium cynomolgi (Pc) is one of the few parasite species that forms quiescent liver stage parasites known as hypnozoites and is therefore a suitable model for Plasmodium vivax . Very little is known about liver stage dormancy, which hampers the search for compounds with anti-hypnozoite activity. Here, we present the development of a Pc in vitro infection model using stem cell-derived hepatocytes from Macaca fascicularis . IPS cells were established on feeder free condition and differentiated into hepatocytes via inducible overexpression of key transcription factors. The generated hepatocytes were infected with Pc sporozoites and hypnozoite formation as well as schizont development were confirmed by immunofluorescence. This system is a promising tool to study the mechanisms underlying liver stage dormancy and facilitate drug discovery against hypnozoites.