Simian iPS-derived hepatocytes support Plasmodium cynomolgi infection and hypnozoite formation.

INTRODUCTION: Plasmodium cynomolgi is one of the few malaria parasite species that forms dormant liver stages known as hypnozoites and is therefore a suitable model for Plasmodium vivax, the causative agent of recurrent malaria. Very little is known about the biology and pharmacology of liver stage dormancy, which hampers the search for compounds with anti-hypnozoite activity. METHODS: We present the development of a P. cynomolgi in vitro infection model using stem cell-derived hepatocyte-like cells from Macaca fascicularis. iPS cells were established on feeder free condition and differentiated into hepatocyte-like cells via inducible overexpression of key transcription factors. RESULTS: The generated cells were infected with P. cynomolgi sporozoites, and hypnozoite formation as well as schizont development were confirmed by immunofluorescence microscopy. DISCUSSION: This simian iPS-derived model is a promising alternative to current P. vivax in vitro infection systems to study the mechanisms underlying liver stage dormancy.