Hematopoietic Stem Cell Function in a Murine Model of Sickle Cell Disease
Figure 4
Functional defect of sickle hematopoietic stem cells in a competitive repopulation assay. Strategy for sorting KSL cells from whole bone marrow: mononuclear cells gated on FSC and SSC of whole BM (a), gated lineage and propidium iodide negative on mononuclear cells (b), and c-kit+, Sca1+, Lin− (KSL) cells (c). Peripheral blood engraftment after transplantation. Representative flow cytometry plots showing KSL cells from control mice engrafted at 15% (d), sickle KSL cells engrafted at 3% (e), and NAC- treated sickle KSL cells engrafted at 9% (f). Composite data showing a reduced capacity for engraftment between hemizygous and control mice and a further defect in KSL cells from homozygous mice 24 weeks after transplant (g). Graphical representation of the data from all mice: pretreatment of donor cells with NAC partially restored engraftment of KSL cells from homozygous sickle cell mice.
