SHORT-TERM AND LONG-TERM MULTILINEAGE REPOPULATING HEMATOPOIETIC STEM-CELLS IN LATE FETAL AND NEWBORN MICE - MODELS FOR HUMAN UMBILICAL-CORD BLOOD

Blood from late fetal and newborn mice is similar to umbilical cord bl ood obtained at birth in human beings, an important source of stem cel ls for clinical transplantation. The mouse model is useful because lon g-term functions can be readily assayed in vivo. To evaluate the funct ions of hematopoietic precursors in the blood and other tissues of lat e fetal and newborn mice, short- and long-term multilineage repopulati ng abilities were measured in vivo by competitive repopulation. Manipu lations that might affect cell function, such as enrichment, tissue cu lture, or retroviral marking, were avoided. Hematopoietic stem cell fu nctions of late fetal or newborn blood, liver, and spleen, were assaye d as myeloid and lymphoid repopulating abilities relative to standard adult marrow cells. Donor cells from these tissues as well as adult co ntrol donor marrow cells were all of the same genotype. Cells from eac h donor tissue were mixed with portions from a pool of standard adult ''competitor'' marrow distinguished from the donors by genetic differe nces in hemoglobin and glucosephosphate isomerase. After 21 to 413 day s, percentages of donor type myeloid and lymphoid cells in recipient b lood were measured to assay the functional abilities of donor precurso rs relative to the standard. These relative measures are expressed as repopulating units, where each unit is equivalent to the repopulating ability found in 100,000 standard adult marrow cells. Thus, measures o f repopulating units do not compare single cells but overall repopulat ing abilities of donor cell populations. Relative functional abilities in 1 million nucleated cells from late fetal or newborn blood were se veral times less than those found in adult marrow, but far more than i n normal adult blood, and appeared to include long-term functional pri mitive hematopoietic stem cells (PHSC) similar to those in marrow. To estimate functional abilities of individual PHSC, variances among larg e groups of identical recipients were analyzed using both the binomial model and competitive dilution, a new model based on the Poisson dist ribution. The data best fit the hypothesis that individual PHSC from a dult marrow, late fetal blood, or newborn blood each produce similar f ractions of the total lymphoid and erythroid cells found in the recipi ent for many months. (C) 1997 by The American Society of Hematology.