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Characterization of Selectin Ligands on Hematopoietic Stem CellsMahmood, Hanan S. 18 May 2013 (has links)
Successful bone marrow (BM) transplantation requires the homing of the transplanted
hematopoietic stem/progenitor cells (HSPCs) to their bone marrow niche, where they
undergo differentiation to form mature cells that are eventually released into the
peripheral blood. However, the survival rate of patients receiving BM transplants is poor
since many of the transplanted HSPCs do not make it to their BM niches in the
recipient’s body. Since the availability of HSPCs from traditional sources is limited,
transplanting more number of HSPCs is not a solution to this problem. This study aims to
characterize the adhesion molecules mediating cell migration in order to better
understand the adhesion mechanisms of HSCs with the bone marrow endothelium. This
will aid in developing future tools to improve the clinical transplantation of HSPCs. This
study also aims to understand the factors that influence HSPC proliferation in the bone
marrow niche.
E-selectin plays an important role in the process of homing; however, its ligands on
HSPCs are not well characterized. We used western blotting and immunoprecipitation to
show that endomucin is expressed on HSPCs and plays a role in the binding of HSPCs to
E-selectin. We also studied the effect of recombinant E-selectin on the expression of a
newly characterized E-selectin ligand in our lab, CD34, in HSPCs. This will provide us
insight into novel roles for endomucin and E-selectin and help us to understand the
factors influencing HSPC migration to BM endothelium.
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