Ex vivo manipulation of umbilical cord blood-derived hematopoietic stem/progenitor cells with recombinant human stem cell factor can up-regulate levels of homing-essential molecules to increase their transmigratory potential

Objective. The cause of delayed hematopoietic reconstitution after umbilical cord blood transplantation (UCBT) remains controversial. We hypothesized that hematopoietic stem/progenitor cells (HS/PCs) from UCB have some defects of the homing-related molecules responsible for their slow engraftment. Materials and Methods. A homing-related molecule repertoire expressed on HS/PCs from fresh and cryopreserved UCB, mobilized peripheral blood (mPB), and bone marrow (BM) were compared using sensitive, four-color fluorescence-activated cell sorting analysis. Purified CD34⁺ cells were subjected to ex vivo transmigration through double-coated transwell filter inserts, and an in vivo homing assay was performed in xenotransplanted NOD/SCID mice. Results. UCB-derived CD34^bright cells expressed significantly lower levels of CD49e, CD49f, and CXCR-4 than their mPB and BM counterparts. CD34⁺ cells from UCB (and BM) exhibited significantly lower ex vivo transmigration than those from mPB, which were largely blocked by neutralizing antibodies to CD49e or CD49f. Recombinant human tumor necrosis factor-α treatment enhanced ex vivo transmigration of CD34⁺ cells from UCB and BM by inducing expression of the matrix metalloproteinases MMP-2/MMP-9. Short-term treatment of UCB-derived CD34⁺ cells with rHu-stem cell factor (rHuSCF) up-regulated levels of the homing-related molecules with their increased ex vivo transmigratory and in vivo homing potential. Conclusion. Our results indicate that disadvantageous transmigratory behavior of HS/PCs from UCB, which might partly explain the delayed reconstitution after UCBT, can be reversed by ex vivo manipulation with rHuSCF.