Transplantation studies using nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) mice ( 11) as recipients have identified a population of SCID-repopulating cells (SRC) present in human umbilical cord blood (CB), bone marrow, and growth factor mobilized peripheral blood progenitor cells (PBPC) ( 12– 18). Over the last 8 years, however, several different xenotransplantation models have been developed that will facilitate investigation into the relationship of different populations and begin to define the hierarchy of the human hematopoietic system. Rather, some multipotential cells appear to represent a somewhat more advanced population with a limited engraftment potential.Ĭomparable dissection of the structure of the human hematopoietic system has not been possible in the past, given the lack of appropriate systems for experimental transplantation. Although LTRSC are multipotential, evidence now suggests that not all multipotential cells are LTRSC ( 8, 10). Multipotentiality, the ability to generate multiple blood-cell lineages including myeloid, erythroid, and lymphoid was at one time also considered to be a characteristic unique to the LTRSC. These primitive cells, referred to as long-term repopulating stem cells (LTRSC), are distinguished from other repopulating cells, by their capacity to self-replicate through a process known as self-renewal ( 1). Findings from numerous studies indicate that precursors with repopulating potential represent a developmental continuum, ranging from relatively mature cells with short-term repopulating potential to the most primitive cells able to provide sustained, long-term engraftment ( 3, 10). Transplantation studies using retrovirus-marked cells or populations isolated based on specific cell surface molecules have provided compelling evidence for heterogeneity within the subset of precursors with repopulating potential ( 3– 9). Our understanding of the hierarchical structure within the early developmental stages of the hematopoietic system have been largely defined by findings from experimental manipulations in the mouse ( 1, 2). 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. Additionally, a much higher frequency of T cell precursors are found among SCID-repopulating cells in the CD34 +/CD38 − subpopulation.
Nod scid mice serial#
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. CD34 +/CD38 + progenitors can repopulate recipients rapidly, but can only maintain the graft for 12 weeks or less and have no secondary repopulation potential. 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. 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. The nonobese diabetic/severe combined immunodeficiency (SCID) mouse has been a particularly useful model. 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.
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