TY - JOUR
T1 - Differential long-term and multilineage engraftment potential from subfractions of human CD34+ cord blood cells transplanted into NOD/SCID mice
AU - Hogan, Christopher J.
AU - Shpall, Elizabeth J.
AU - Keller, Gordon
PY - 2002/1/8
Y1 - 2002/1/8
N2 - 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 system in 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 longterm potential of human precursors can be evaluated in the mouse model.
AB - 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 system in 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 longterm potential of human precursors can be evaluated in the mouse model.
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U2 - 10.1073/pnas.012336799
DO - 10.1073/pnas.012336799
M3 - Article
C2 - 11782553
AN - SCOPUS:0037039361
SN - 0027-8424
VL - 99
SP - 413
EP - 418
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 1
ER -