Plasmodium vivax is the most widely distributed human malaria parasite with tropism for reticulocytes, immature red blood cells that during their differentiation to erythrocytes secrete extracellular vesicles (EVs). The spleen (SP) plays an important role in vivax malaria as it contains the largest parasite biomass during chronic infections. Previous reports demonstrated that circulating EVs from infections act as intercellular communicators in vitro facilitating parasite’s cyto-adherence to the human spleen. Additionally, the bone marrow (BM) has been reported as another major source of cryptic parasites accounting for asymptomatic infections. Therefore, the generation of a humanized SP and BM mouse model would represent a major breakthrough to study the role of EVs as intercellular communicators in these organs in vivo.
Human BM CD34+ cells were engrafted in busulfan treated immunodeficient NSG mice to achieve humanization. Mice were treated with hIL-3 and hEPO to get differentiation through human erythrocytic linage. Low numbers of hCD71+ cells were detected by flow cytometry as well as human genes expression for erythroid-specific transcription factors. Immunofluorescence assays only revealed murine erythropoietic islands in the BM. Due to these results we have implemented the use of human fetal tissue sources of the bone marrow and spleen (Ethical approval CEIC PI-21-178), Biobanc IGTP-HUGTP, Institut d’Investigació Germans Trias i Pujol, Badalona, Barcelona, Spain) to engraft in immunodeficient recipients. Moreover, we are currently implementing the engraftment of hCD34+ cells into another immunodeficient strain that supports the engraftment without the need for any treatment. Construction of such models representing these human erythroid organs should advance P. vivax research.