Differential long-term and multilineage engraftment potential from subfractions of human CD34+ cord blood cells transplanted into NOD/SCID mice.
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 long-term potential of human precursors can be evaluated in the mouse model.
Hogan
Christopher J
CJ
Bone Marrow Transplant Program, Division of Medical Oncology, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, USA. chris.hogan@uchsc.edu
Shpall
Elizabeth J
EJ
Keller
Gordon
G
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000096:biosynthesis*; D000943:Antigens, Differentiation / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000378:metabolism; D019070:Cell Lineage; D002469:Cell Separation; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008562:Membrane Glycoproteins; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009244:NAD+ Nucleosidase / Q000096:biosynthesis; D011485:Protein Binding; D013347:Subcellular Fractions / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology; D013997:Time Factors
D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D017493:Leukocyte Common Antigens; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; C498155:Cd38 protein, mouse; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1