SCF modulates organ distribution and hematopoietic engraftment of CB-derived pluripotent HPC transplanted in NOD/SCID mice

Abstract

BACKGROUND: During the engraftment process of transplanted HPC, the beta 1 integrins play an important role. An increased expression and adhesive function of these integrins has been shown in hematopoietic cell lines and peripheral blood-derived HPC after stimulation with SCF. In this study, we investigated the influence of SCF on the engraftment capability and tissue distribution of cord blood (CB) cells transplanted into NOD/SCID mice. METHODS: CB-derived mononuclear cells were injected i.v. into 40 sublethally irradiated NOD/SCID mice with or without the addition of 10 microg SCF/ mouse. Six weeks later, BM, liver, kidneys, brain and testicular tissue were analyzed for the prevalence of human cells. RESULTS: The mean proportion of human CD45+ CD71+ cells within the BM of all engrafted mice receiving SCF in addition to the cells was 1.7-fold higher than in the respective controls. By immunohistochemical staining, human cells were found in liver and kidneys of the engrafted animals, but not in neural tissues or testicles. In the kidneys, the proportion of human cells rose significantly from 0.07 +/- 0.3% to 0.24 +/- 0.05% with treatment with SCF, compared with untreated controls. Single human cells in the liver additionally stained positive for human albumin, indicating organ-specific differentiation of the transplanted cells. DISCUSSION: Our results indicate that stimulation with SCF modulates the tissue distribution of the progeny of the transplanted cells and improves the hematopoietic engraftment potential of transplanted CB cells.