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Project

Karakterisatie van moleculaire mechanismen die hematopoietische reconstitutie van hematopoietische stamcellen verhogen.

The overarching goal of this proposal is to increase the number of "engrafting hematopoietic stem cells (HSC)" from umbilical cord blood (UCB), whose use is restricted to smaller patients due to the limited number of HSC present in the each unit. To enhance the blood reconstitution ability of a given number of HSC, present within e.g. one unit of UCB, can include developing methods to increase absolute HSC expansion, and/or achieve absolute HSC homing. One way to increase the number of "engraftable HSC" form e.g. UCB, is by increasing the HSC homing efficiency. The advantage of this approach over inducing ex vivo HSC expansion is that HSC will be minimally or not altered. Hence the chance for lineage skewing, late graft failure due to exhaustion of the primitive HSC compartment, or culture induced genetic abnormalities can be minimized. We propose further evaluation of the hypothesis that two "clinically approved" molecules, i.e. TFPI and BMP4, improve HSC homing. Studies will be carried out to define the mechanisms underlying the ligand mediated improved homing; and we will test if these clinical grade molecules improve homing of human HSC. In a third aim, we will perform studies to identify additional candidate receptor-ligand pairs that may improve HSC homing.
Datum:1 jan 2011 →  31 dec 2016
Trefwoorden:Hematopietic stem cells, Umbilical cord blood