Bone marrow cell trafficking following intravenous administration

To address trafficking of transplanted marrow cells immediately after intra venous infusion, we examined the early fate of infused non-adherent, low-de nsity donor bone marrow cells in a syngeneic mouse model. The presence of i nfused donor cells, marked with indium-111 oxine (In-111), with the fluores cent dye PKH26, or by a detectable transgene marker, was evaluated at 3-48 h in a variety of tissues, including peripheral blood, All three cell-marki ng methods indicated a rapid (< 4 h) influx of cells into the bone marrow, liver, spleen, muscle and other tissues. Moreover, these tissues remained p ositive for the 48 h observation period. Interestingly, analysis of PKH26-p ositive cells in non-myeloablated animals demonstrated that approximately 1 7% of infused donor marrow cells localized to the marrow space within 15 h, whereas a smaller proportion of donor cells (similar to 1-2%) localized to the marrow in recipients preconditioned by irradiation, In an effort to en rich for cells that specifically home to the bone marrow, PKH26-labelled do nor marrow cells were recovered from the first host and infused into a seco ndary recipient. Although this was a phenotypically undefined population of cells, no increase was observed in the relative fraction of PKH26-labelled cells returning or 'homing' to the marrow of the second recipient. Taken t ogether, these data suggest both that marrow engraftment may be mediated by non-specific 'seeding' rather than a specific homing signal, and that effi cient targeting of transplanted cells to the marrow is a complex multifacet ed process.