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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.

Hematopoietic Stem/Progenitor Cell Sources to Generate Reticulocytes for Plasmodium vivax Culture