Primitive hematopoietic stem cell function in vivo is uniquely high In theCXB-12 mouse strain

Bone marrow cells (BMCs) from CXB-12/HiaJ (CXB-12) mice had 14 times the to tal long-term repopulating ability found in the best of 11 other CXB recomb inant inbred (RI) lines. BMCs from each RI line donor were mixed with genet ically marked standard competitor BMCs from the BALB/cBy x C57BL/6 F1 (CByB 6F1) hybrid, the mice used to produce the RI lines, and the mixtures repopu lated lethally irradiated CByB6F1 recipients. Percentages of donor-type ery throcytes and lymphocytes measured the actual long-term repopulating functi ons of the donor RI lines relative to the standard competitor. CXB-12 BMCs repopulated better after 3 or 6 months than after 1 month, suggesting that the most primitive precursors were involved, compared to CByB6F1 standard c ompetitor cells, CXB-12 cells repopulated 3 to 12 times as well, with their advantage increasing when higher doses of cells were transplanted, probabl y because of hybrid resistance of the recipient against low doses. This was far better than expected, because F1 cells normally function 2 to 3 times as well as cells from an inbred strain. In competitive dilution, the advant age resulted from 2 factors: more precursor cells and more function per pre cursor. In the model that best fit the data, CXB-12 donors had 2.4 times th e concentration of hematopoietic stem cells (HSCs) as the CByB6F1 standard, and each HSC repopulated 1.4 times as well. CXB-12 mice did not have eleva ted erythrocyte and lymphocyte numbers in blood and marrow and did not have unusually elevated concentrations of colony forming unit spleen, cobblesto ne colonies, and long-term colony-initiating cells in marrow, (C) 2000 by T he American Society of Hematology.