TOWARDS SUCCESSFUL ADAPTATION OF PLASMODIUM KNOWLESI TO LONG-TERM IN-VITRO CULTURE IN HUMAN ERYTHROCYTES

Plasmodium knowlesi, a simian malaria parasite, is widely used as a malaria model and now characterized as a clinically significant parasite that can lead to outbreaks throughout most countries in Southeast Asia. Despite its importance, both fundamental and clinical studies of P. knowlesi have been impeded by the lack of a convenient in-vitro culture system partly due to the parasite’s preference for reticulocytes. Due to a limited number of reticulocytes that could be collected from fresh sources such as umbilical cord, bone marrow, and peripheral blood, scientists have opted reticulocytes generated from CD34⁺ hematopoietic stem cells (HSCs) that have been cultured in an in-vitro system. With sufficient growth factors (GFs) and differentiation factors (DFs), a higher number and more homogenous populations of reticulocytes could be obtained from HSCs in-vitro. Here, we review an approach to produce massive expansion of CD34⁺ HSCs and their differentiation into reticulocytes that could be used for the establishment of a continuous in-vitro culture of P. knowlesi or P. vivax. The successful development of the long-term in-vitro culture of this parasite could ultimately provide an ideal system for forwarding diagnostic, anti-malarial drug and vaccine studies in malaria.