Experimental hematology
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Experimental hematology · Jun 2002
Ex vivo expanded cord blood cells provide rapid engraftment in fetal sheep but lack long-term engrafting potential.
Cord blood (CB) products are becoming routinely used in unrelated allogeneic transplantation for smaller pediatric patients. Because of the low numbers of cells in CB compared to bone marrow or peripheral blood progenitor cells, their use is more limited in larger adults. Therefore, we developed ex vivo expansion conditions for CB and currently are transplanting ex vivo expanded CB products to patients receiving high-dose chemotherapy. As there is concern that ex vivo expansion may exhaust long-term engrafting cells, the current clinical protocols consist of both an expanded fraction and an unexpanded fraction. To determine the effect of expansion culture on long-term engrafting cells, we evaluated the short- and long-term engrafting potential of ex vivo expanded CB using a fetal sheep xenogeneic transplant model. ⋯ Ex vivo expansion of CB CD34(+) cells under the conditions described results in the generation of increased mature cells and progenitors that are capable of more rapid engraftment in fetal sheep compared to unexpanded CB CD34(+) cells. The expanded cells engrafted primary sheep but lacked secondary and tertiary engrafting potential. These studies demonstrate that although ex vivo expanded cells may be able to provide rapid short-term engraftment, the long-term potential of expanded grafts may be compromised. Therefore, clinical protocols may require transplantation of two fractions of cells, an expanded CB graft to provide rapid short-term engraftment and an unmanipulated fraction of CB graft to provide stem cells for long-term engraftment.