ESTABLISHMENT OF A HUMAN HEPATOCYTE LINE THAT SUPPORTS IN VITRO DEVELOPMENT OF THE EXO-ERYTHROCYTIC STAGES OF THE MALARIA PARASITES PLASMODIUM FALCIPARUM AND P. VIVAX

JETSUMON SATTABONGKOT Department of Entomology, and Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Surgery Department, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Department of Pathobiology, Mahidol University, Bangkok, Thailand; Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania

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NONGNUCH YIMAMNUAYCHOKE Department of Entomology, and Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Surgery Department, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Department of Pathobiology, Mahidol University, Bangkok, Thailand; Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania

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SURASAK LEELAUDOMLIPI Department of Entomology, and Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Surgery Department, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Department of Pathobiology, Mahidol University, Bangkok, Thailand; Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania

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MANEERAT RASAMEESORAJ Department of Entomology, and Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Surgery Department, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Department of Pathobiology, Mahidol University, Bangkok, Thailand; Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania

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RACHANEEPORN JENWITHISUK Department of Entomology, and Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Surgery Department, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Department of Pathobiology, Mahidol University, Bangkok, Thailand; Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania

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RUSSELL E. COLEMAN Department of Entomology, and Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Surgery Department, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Department of Pathobiology, Mahidol University, Bangkok, Thailand; Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania

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RACHANEE UDOMSANGPETCH Department of Entomology, and Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Surgery Department, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Department of Pathobiology, Mahidol University, Bangkok, Thailand; Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania

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LIWANG CUI Department of Entomology, and Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Surgery Department, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Department of Pathobiology, Mahidol University, Bangkok, Thailand; Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania

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THOMAS G. BREWER Department of Entomology, and Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Surgery Department, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Department of Pathobiology, Mahidol University, Bangkok, Thailand; Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania

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Our understanding of the biology of malaria parasite liver stages is limited because of the lack of efficient in vitro systems that support the exo-erythrocytic (EE) development of the parasite. We report the development of a new hepatocyte line (HC-04) from normal human liver cells. The HC-04 cells have proliferated in hormone-free medium for more than 200 passages. The cells were hyperdiploid, resembled liver parenchymal cells, and synthesized major liver-specific proteins and enzymes. Using Plasmodium falciparum and P. vivax sporozoites harvested from salivary glands of infected mosquitoes, we showed that HC-04 cells supported the complete EE development of these two most prevalent human malaria parasites. The EE parasites attained full maturation as shown by their infectivity to human erythrocytes. The infection rates of the liver cells were estimated to be 0.066% and 0.041% for P. falciparum and P. vivax, respectively. As the first human hepatocyte line known to support complete EE development of both P. falciparum and P. vivax, HC-04 will provide an experimental model that can be used for studying the biology of liver stage malaria parasites.

Author Notes

Reprint requests: Jetsumon Sattabongkot, Department of Entomology, Armed Forces Research Institute of Medical Sciences, 315/6 Rajvithi Road, Bangkok 10499, Thailand, Thailand, Telephone 66-2-644-5777, Fax 66-2-354-7885, E-mail: JetsumonP@afrims.org or Liwang Cui, Department of Entomology, The Pennsylvania State University, University Park, PA, 16802, Telephone: 814-863-7663, Fax: 814-865-3048, E-mail: luc2@psu.edu.
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