Characterization of a hematopoietic stem cell with engraftment advantage

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Exp Hematol 2000 Dec; 28(12):1498.


In studying hematopoietic stem cell (HSC) function in vivo, we discovered that HSCs from CXB-12/HiaJ (CXB-12) mice have 14 times the total long term repopulating ability found in the best of 11 other CXB recombinant inbred (RI) lines. This was determined using the competitive repopulation assay where bone marrow cells (BMCs) from each RI line donor were mixed with gentically marked competitor BMCs from the (BALBx B6) F1 (F1) hybrid, the mice used to produce the RI lines, and the mixtures repopulated lethally irradiated F1 recipients. After six months, percentages of donor type erythrocytes and lymphoytes gave a measure of the long term repopulating abilities of the donor RI lines relative to the F1 competitor. When high doses of BMCs were used, CXB-12 cells repopulated 6-12 times better than the F1 competitor cells, while when a low dose of BMCs were used in competitive dilution, CXB-12 donors had 2.4 times the number of HSCs as the F1 competitor, and each CXB-12 HSC repopulated 1.4 times as well. The CXB-12 HSC engraftment advantage is associated with a 50% increase in cobblestone area forming cell frequency and an one fold increase in the number of side population cells revealed by Hoechst 33342 vital dye staining. There was no effect on day 12 spleen colony forming units. The CXB-12 HSC engraftment advantage appears to result from increased HSC proliferation and differentiation abilities which are caused either by a unique recombination of parental genes or by specific mutations in the CXB-12 genome.

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