Differential long-term and multilineage engraftment potential from subfractions of human CD34+cord blood cells transplanted into NOD/SCID mice

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Abstract
Over the past decade xenotransplantation systems have been used with increasing success to gain a better understanding of human cells that are able to initiate and maintain the hematopoietic systemin vivo. The nonobese diabetic/severe combined immunodeficiency (SCID) mouse has been a particularly useful model. Human cells capable of hematopoietic repopulation in this mouse, termed SCID-repopulating cells, have been assumed to represent the most primitive elements of the hematopoietic system, responsible for long-term maintenance of hematopoiesis. However, we demonstrate that SCID-repopulating cells present in the CD34+cell fraction of cord blood can be segregated into subpopulations with distinct repopulation characteristics. CD34+/CD38+progenitors can repopulate recipients rapidly, but can only maintain the graft for 12 weeks or less and have no secondary repopulation potential. Conversely, the more primitive CD34+/CD38−subpopulation repopulates recipients more gradually, can maintain the graft for at least 20 weeks, and contains cells with serial repopulation potential throughout the engraftment period. Additionally, a much higher frequency of T cell precursors are found among SCID-repopulating cells in the CD34+/CD38−subpopulation. These findings demonstrate that cells with variable repopulation potential comprise the human CD34+population and that short- and long-term potential of human precursors can be evaluated in the mouse model.