BALB/c Rag2 2/2 IL-2Rcc 2/2 mice were bred and maintained in individual ventilated cages, and fed with autoclaved food and water. HIS mice were generated as previously described [13, 14, 15, 16] , with the approval of the Animal Ethical Committee of the AMC-UvA (permit number DHL-100970). In brief, human fetal livers were obtained from elective abortions with gestational age ranging from 14 to 20 weeks. Magnetic enrichment of CD34 + cells (.98% pure) was performed by using the CD34 Progenitor Cell Isolation kit (Miltenyi Biotech), after preparation of single cell suspensions and isolation of mononuclear cells by density gradient centrifugation over Lymphoprep (Axis Shield). Finally, newborn (,5 days old) sub-lethally irradiated (3.5 Gy) BALB/c Rag2 2/2 IL-2Rcc 2/2 mice were injected via intra-hepatic route with 5-10610 4 sorted CD34 + CD38 2 human fetal liver hematopoietic stem cells in 30 ml. All manipulations of HIS mice were performed under laminar flow. Cell suspensions were prepared in RPMI medium supplemented with 2% fetal calf serum (FCS).