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Hematopoietic Stem/Progenitor Cell Sources to Generate Reticulocytes for Plasmodium vivax Culture
Authors:Florian Noulin  Javed Karim Manesia  Anna Rosanas-Urgell  Annette Erhart  Céline Borlon  Jan Van Den Abbeele  Umberto d'Alessandro  Catherine M Verfaillie
Institution:1. Unit of Malariology, Institute of Tropical Medicine, Antwerp, Belgium.; 2. Department of development and regeneration, Stem Cell Institute, Leuven, Belgium.; 3. Unit of Veterinary Protozoology, Institute of Tropical Medicine, Antwerp, Belgium.; 4. Medical Research Council Unit, Fajara, The Gambia.; Instituto de Higiene e Medicina Tropical, Portugal,
Abstract:The predilection of Plasmodium vivax (P. vivax) for reticulocytes is a major obstacle for its establishment in a long-term culture system, as this requires a continuous supply of large quantities of reticulocytes, representing only 1–2% of circulating red blood cells. We here compared the production of reticulocytes using an established in vitro culture system from three different sources of hematopoietic stem/progenitor cells (HSPC), i.e. umbilical cord blood (UCB), bone marrow (BM) and adult peripheral blood (PB). Compared to CD34+-enriched populations of PB and BM, CD34+-enriched populations of UCB produced the highest amount of reticulocytes that could be invaded by P. vivax. In addition, when CD34+-enriched cells were first expanded, a further extensive increase in reticulocytes was seen for UCB, to a lesser degree BM but not PB. As invasion by P. vivax was significantly better in reticulocytes generated in vitro, we also suggest that P. vivax may have a preference for invading immature reticulocytes, which should be confirmed in future studies.
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