EARLY TRANSPLANTATION TO A NORMAL MICROENVIRONMENT PREVENTS THE DEVELOPMENT OF STEEL HEMATOPOIETIC STEM-CELL DEFECTS

Our previous results showed that hematopoietic stem cells from 16-week -old Sl/Sl(d) mice are not as competitive as congenic +/+ control stem cells. Possible explanations for these findings are that the Steel st em cells are either inherently defective or lose competitive ability b y residence in an environment lacking membrane-bound Steel factor. Ln the present report, any long-term effects of the Steel microenvironmen t were eradicated by transferring neonatal Sl(d)/Sl(d) marrow and sple en cells into an irradiated but otherwise normal adult hematopoietic m icroenvironment. Host cells were completely replaced by donor cells wi thin 6 weeks. Eight months after transplantation, the Sl(d)/Sl(d) and similarly treated +/+ littermate control cells from tile primary recip ient marrow were competed against genetically marked normal cells in a n irradiated secondary host. The Steel cells were as competitive as th e control cells demonstrating that Steel stem cells are not inherently defective. Results suggest that the stem cells, when retained in the mutant environs into adulthood, are either reduced in number or phenot ypically altered by lack of the membrane-bound Steel factor.