Development and aging of primitive hematopoietic stem cells in BALB cBy mice

Evaluating the function of an individual hematopoietic stem cell (HSC) is a difficult and important problem, The functional ability per FISC, as well as the HSC concentration, was measured with minimal disruption to the cells in vivo using the new competitive dilution assay. Distribution of HSC into recipients was modeled based on Poisson probabilities. Predictions of dono r contributions front models assuming different levels of donor HSC functio nal ability and concentration were compared to actual observations. The mod el with the least difference between predictions and observations was accep ted. In BALB/cBy (BALB) mice, models assuming equal functional ability of H SC from the same donor fit extremely well with actual observations, suggest ing that all HSC are functionally homogeneous at any particular time point during development or aging. Relative HSC functional ability per cell decli ned during development, so that a fetal HSC had 1.6 to 3.0 times the functi onal ability of a young adult HSC. The decline continued with age, so that a young adult HSC had 1.6 to 2.0 times the functional ability of an old HSC , Concentrations of HSC that engrafted and functioned were similar among 16 -day fetal liver cells and bone marrow cells (BMC) from 3-month and 25 to 2 8-month-old adult mice. They were either 10 or 4 HSC per million cells when tested in BALE or CByD6F1 recipients, respectively, All HSC were pluripote nt and produced lymphoid and myeloid descendants proportionally (r = 0.80 t o 0.98, p < 0.01), Fetal and young HSC in both types of recipients maintain ed clonal stability long term so that percentages of donor cells at 6 and 9 months were strongly correlated (r = 0.72 to 0.93, p < 0.01), Although HSC from aged donors in BALE recipients maintained clonal stability, HSC from the same aged donors failed to show clonal stability in CByB6F1 recipients, perhaps due to the less suitable host environment, All HSC from BALE mice seemed to have equal functional levels at a given stage of life and were gr adually exhausted simultaneously through development and aging. (C) 1999 In ternational Society for Experimental Hematology. Published by Elsevier Scie nce Inc.