Similar repopulating capacity of mitotically active and resting umbilical cord blood CD34+ cells in NOD/SCID mice

Abstract

It was hypothesized that during mammalian development, the extensive need for hematopoietic cells requires equal contribution to blood cell production from both quiescent and cycling hematopoietic stem cells (HSCs) while maintaining the stem cell pool. To investigate this hypothesis, the engraftment potential of umbilical cord blood (UCB) CD34+ cells residing in either G0(G0CD34+ cells) or G1(G1CD34+ cells) phases of the cell cycle was assessed in nonobese diabetic/severe combined immune-deficient (NOD/SCID) mice. Whereas the level of chimerism in mice transplanted with UCB G0CD34+ cells was 69.9% ± 24.0%, mice receiving equal numbers of G1CD34+ cells harbored 46.7% ± 21.3% human cells 8 weeks posttransplantation. Both groups of cells sustained multilineage differentiation and the production of CD34+cells in recipient animals. The relationship between the number of transplanted G0CD34+ or G1CD34+ cells and the level of chimerism was analyzed by a general linear models procedure. Although the initial level of chimerism following transplantation of G0CD34+ cells was higher than that sustained by G1CD34+ cells, the increment in the degree of chimerism obtained with each additional 103 cells of either phenotype was identical, suggesting that the reconstitution potential of these 2 types of cells was similar. Of interest is that human cells recovered from primary recipients of both G0CD34+ and G1CD34+cells engrafted in secondary NOD/SCID recipients, albeit at a substantially lower level, confirming the primitive nature of UCB CD34+ cells residing in G1.