Long-term erythropoietic repopulating ability of old, young, and fetal stem cells.

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Abstract
The competitive repopulation assay was used to test long-term stem cell function by directly comparing how well competing stem cells repopulate a recipient and produce differentiated cell types. C57BL/6J (B6) mice were used as donors, while recipients and competitors were WBB6F1 hybrids with genetically distinguishable Hb. Lethally irradiated young WBB6F1 recipients were given a mixture of 2.5 .times. 106 cells from B6 old marrow, young marrow, or fetal liver donors; each recipient also recieved a standard dose of 1 .times. 106 marrow cells from a pool of young WBB6F1 competitors. The old marrow cells competed the best in repopulating the recipients. This pattern was maintained even after recovery from sublethal irradiation, a treatment that severely stresses stem cells. This stress was demonstrated when sublethal irradiation caused a 20-fold decline in repopulating ability measured using Hb markers and a 3- to 7-fold decline using chromosome markers. Stem cells from old marrow competed better than young or fetal cells in similar experiments using immunologically crippled recipients or using unirradiated W/Wv recipients that are immunologically intact. In both types of recipients, the advantage of old marrow cells again persisted after recovery from sublethal irradiation. Other genotypes were tested, and marrow cells from old B6CBAF1 donors competed better than those from young donors of that genotype. Marrow cells from young CBA donors competed better than those from old CBA donors. Apparently, stem cells do not age, and regulatory changes with age may promote rapid stem cell repopulation in B6 and B6CBAF1 mice, but inhibit it in CBA mice.