Plasma from poorly mobilizing human subjects inhibits cytokine-induced murine blood stem-cell mobilization

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, GM-CFC and HPP-CFC per spleen in murine recipients of these plasma samples. Overall, there was a positive association between transforming growth factor β (TGF-β) levels and CD34⁺ cells per liter of blood processed (LBP). However, when arbitrarily segregated into good versus poor mobilizer, 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-β levels was found. For 11 individuals whose plasma, based on colony assays, enhanced mobilization when injected into mice, no correlation with TGF-β levels was evident. Discussion: Elevated plasma TGF-β levels in some stem-cell donors may be associated with poor stem-cell mobilization. It remains to be determined whether elevation of TGF-β levels is a cause of, or a compensatory response to, poor mobilization.