Early production of human neutrophils and platelets posttransplant isseverelycompromised by growth factor exposure.

Abstract

The critical human cells that produce neutrophils and platelets within 3weeks in recipients of hematopoietic transplants are thought to produce these mature blood cells with the same kinetics in sublethally irradiated immunodeficient mice. Quantification of their numbers indicates their relative underrepresentation in cord blood (CB), likely explaining the clinical inadequacy of single CB units in rescuing hematopoiesis in myelosuppressed adult patients. We here describe that exposure of CD34(+) CB cells exvivo to growth factorsthat markedly expand their numbers and colony-forming cell content also rapidly (within 24hours) produce a significant and sustained net loss of their original short-term repopulating activity. This loss of short-term invivo repopulating activity affects early platelet production faster than early neutrophil output, consistent with their origin from distinct input populations. Moreover, this growth factor-mediated loss is not abrogated by published strategies to increase progenitor homing despite evidence that the effect on rapid neutrophil production is paralleled in time and amount by a loss of the homing of their committed clonogenic precursors to the bone marrow. These results highlight the inability of invitro or phenotype assessments to reliably predict clinical engraftment kineticsof cultured CB cells.