Background: Cytokine-induced mobilization of hematopoietic stem/progenitor cells to the circulation facilitates efficient harvest of blood stem cells by leukapheresis. Up to 30% of autologous, and 10-20% of allogeneic blood stem-cell donors respond poorly to mobilizing cytokines and preliminary studies implicated a circulating inhibitor of mobilization.
Methods: In this study, plasma from 11 allogeneic and 23 autologous stem cell donors was assayed for inhibition of mobilization in mice.
Results: There were significant correlations between CD34(+) cells collected/kg human donor weight and spleen weight, CD34(+) CD45(+) cells, GMCFC and HPP-CFC per spleen in murine recipients of these plasma samples. Overall, there was a positive association between transforming growth factor beta (TGF-beta) levels and CD34(+) cells per liter of blood processed (LBP). However, when arbitrarily segregated into good versus poor mobilizers, based on less or greater than 15 million CD34(+) cells collected per LBP, the majority (64%) of normal donors were good mobilizers. The majority of the poor mobilizers (83%) were patients. For a subset of 12 individuals whose plasma strongly inhibited mobilization in the mouse, a significant positive correlation of the extent of inhibition with TGF-beta levels was found. For 11 individuals whose plasma, based on colony assays, enhanced mobilization when injected into mice, no correlation with TGF-beta levels was evident.
Discussion: Elevated plasma TGF-beta levels in some stem-cell donors may be associated with poor stem-cell mobilization. It remains to be determined whether elevation of TGF-beta levels is a cause of, or a compensatory response to, poor mobilization.