The marrow homing efficiency of murine hematopoietic stem cells remains constant during ontogeny.

Abstract

Several recent studies have established the potential clinical utility of hematopoietic stem cells (HSCs) not only for marrow rescue but also for regenerating diseased or damaged nonhematopoietic tissues. These findings have focused renewed interest in understanding the in vivo trafficking patterns of HSCs from different sources. Previous experiments have suggested that the half-life of HSCs in the circulation is short, although the actual proportion that return to the bone marrow (BM) following transplantation has not been previously quantitated. The present study was undertaken to measure this fraction and compare the values obtained for functionally defined HSCs from adult murine BM and day-14 fetal liver (FL). The number of HSCs that could be recovered from the BM of lethally irradiated mice 24 hours after intravenous injection of Ly-5 congenic BM or FL cells was determined by limiting-dilution competitive repopulating unit (CRU) assays in secondary mice. The marrow seeding efficiency of both adult BM- and FL-CRU able to produce lymphoid and myeloid progeny for 5-26 weeks posttransplant was approximately 10%. FL-CRU generated clones that were approximately threefold larger than those produced by BM-CRU. Interestingly, clones produced by "homed" HSCs were approximately twofold smaller than those produced by freshly isolated HSCs. Differences were also seen in the proportions of lymphoid vs myeloid progeny generated by fresh and homed HSCs. These data suggest common mechanisms regulating the BM homing of long-term repopulating HSCs throughout ontogeny despite subtle differences in the size and composition of the clones they generate.