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Fucosylation of ex vivo expanded cord blood (CB) cells improves engraftment in Nod/SCID mice

      CB is as an alternate stem cell source for patients receiving high dose chemotherapy, however the time to neutrophil and platelet engraftment is delayed compared to BM or PBPC products. We have demonstrated faster engraftment with CB products expanded in MSC co-culture leading to an ongoing phase 3 trial. Also studies have demonstrated that fucoyslation of unmanipulated CB also results in faster engraftment in patients. Therefore we hypothesized that fucosylation of expanded CB may provide faster engraftment. CBs were expanded using co culture on MSCs and expanded cells were fucoyslated with fucosyltransferase (FT) VI. CD34+ cells were isolated from the same CB as a control cell population. Immunodeficient (NSG) mice were injected with CD34+ cells, expanded CB cells, or fucosylated expanded cells. Expansion resulted in an increase of 9 fold of TNC and 116 fold increase in CD34+ cells. The expanded cells resulted in faster engraftment of human (hu) CD45+ cells when injected into NSG mice compared to animlas injected with CD34+ cells. The levels of huCD45 in recipient mice was dose dependent with higher cell doses (140 M) resulting in earlier engraftment of huCD45+ cells with a maximum level of 25% huCD45+ cells in the PB, compared to a lower dose (50 M) which engrafted at less than 1% of huCD45+ cells. Treatment with FTVI resulted in an increase of fucosylation from 72% to 98% CLA+ cells. Animals injected with fucosyalted expanded cells achieved up to 25% huCD45+ cells in the PB compared to non fucosylated expanded cells and the engraftment of human cells was more rapid. These data suggest that fucosylation of expanded CB cells may provide enhanced engraftment in the setting of low cell doses such as CB transplantation. Further studies are being performed to support evaluation of fucosylated expanded CB cells in clinical trials in the near future.
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