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Am. J. Trop. Med. Hyg., 74(5), 2006, pp. 708-715
Copyright © 2006 by The American Society of Tropical Medicine and Hygiene

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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*, NONGNUCH YIMAMNUAYCHOKE, SURASAK LEELAUDOMLIPI, MANEERAT RASAMEESORAJ, RACHANEEPORN JENWITHISUK, RUSSELL E. COLEMAN, RACHANEE UDOMSANGPETCH, LIWANG CUI*, AND 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

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.

Received October 26, 2004. Accepted for publication December 19, 2005.

Acknowledgments: We thank the staff of the Vector Borne Disease Control Training Centre (Saraburi, Thailand) for their help in setting up the field sites, the staff at the Department of Entomology, Armed Forces Research Institute of Medical Sciences for technical assistance, Dr. Jonh B. Sacci, Jr. for suggestions on the IFA technique, and Dr. Fidel Zavala for providing monoclonal antibody HSP70.

Financial support: This study received support from the U.S. Army Medical Research and Materiel Command to (Jetsumon Sattabongkot) and the Fogarty International Center to (Liwang Cui and Rachanee Udomsangpetch) (1D43 TW000657).

* Address correspondence to Jetsumon Sattabongkot, Department of Entomology, Armed Forces Research Institute of Medical Sciences, 315/6 Rajvithi Road, Bangkok 10400, Thailand, E-mail: JetsumonP{at}afrims.org or Liwang Cui, Department of Entomology, The Pennsylvania State University, University Park, PA, 16802. E-mail: luc2{at}psu.edu

Authors’ addresses: Jetsumon Sattabongkot, Nongnuch Yimamnuaychoke, Rachaneeporn Jenwithisuk, Maneerat Rasameesoraj, Russell E. Coleman, and Thomas G. Brewer, Armed Forces Research Institute of Medical Sciences, 315/6 Rajvithi Road, Bangkok 10400, Thailand. Surasak Leelaudomlipi, Surgery Department, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand. Rachanee Udomsangpetch, Department of Pathobiology, Mahidol University, Rama VI Road, Bangkok 10400, Thailand. Liwang Cui, Department of Entomology, The Pennsylvania State University, University Park, PA, 16802.

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{at}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{at}psu.edu.




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