Bone marrow cell trafficking following intravenous administration.
To address trafficking of transplanted marrow cells immediately after intravenous infusion, we examined the early fate of infused non-adherent, low-density donor bone marrow cells in a syngeneic mouse model. The presence of infused donor cells, marked with indium-111 oxine (111In), with the fluorescent 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-marking methods indicated a rapid (< 4 h) influx of cells into the bone marrow, liver, spleen, muscle and other tissues. Moreover, these tissues remained positive for the 48 h observation period. Interestingly, analysis of PKH26-positive cells in non-myeloablated animals demonstrated that approximately 17% of infused donor marrow cells localized to the marrow space within 15 h, whereas a smaller proportion of donor cells (approximately 1-2%) localized to the marrow in recipients preconditioned by irradiation. In an effort to enrich for cells that specifically home to the bone marrow, PKH26-labelled donor marrow cells were recovered from the first host and infused into a secondary 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 together, these data suggest both that marrow engraftment may be mediated by non-specific 'seeding' rather than a specific homing signal, and that efficient targeting of transplanted cells to the marrow is a complex multifaceted process.
Cui
J
J
Howard Hughes Medical Institute, Department of Human Genetics, Ann Arbor, MI, USA.
Wahl
R L
RL
Shen
T
T
Fisher
S J
SJ
Recker
E
E
Ginsburg
D
D
Long
M W
MW
D000818:Animals; D016026:Bone Marrow Transplantation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000502:physiology*; D007262:Infusions, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction / Q000379:methods