Differences in cell cycle kinetics of candidate engrafting cells in human bone marrow and mobilized peripheral blood

Objective. Patients undergoing hematopoietic stem cell transplantation (HSC T) with mobilized peripheral blood (MPB) engraft quicker than those receivi ng bone marrow (BM). Our objective was to determine whether candidate engra fting cells-primitive hematopoietic progenitors (PHPs)-from MPB and BM exhi bit different responses to cytokines that could explain this observation, Materials and Methods. We compared the cell cycle kinetics and ex vivo expa nsion of PHP-enriched cells obtained from MPB (n = 12) and BM (n = 10) by f luorescence-activated sorting of CD90(+), AC133(+) or CD38(dull) subsets of pre-selected CD34(+) cells, Cell cycle status, before and after 40 hours o f serum-free culture with a cytokine cocktail, was assessed bg multiparamet er pow cytometry following incubation with Hoechst 33342 and pyronin Y, Results. We found that 0.2% +/- 0.3% of MPB CD34(+)CD90(+) cells were in SI G,IR I phases at hour 0, compared with 5% +/- 2.5% of those from BM. (p = 0 .0001), and 86.3% +/- 9.7% were in Go, compared with 65.3% +/- 10% of those in BM (p = 0.0001), After 40 hours of culture, CD34(+)CD90(+) cells from M PB were more mitotically active than those from BM, with 29% +/- 4.9% in S/ G(2)/M and 20% +/- 11.34% in G(0), compared to 19% +/- 6.5% (p = 0.001) and 39.2% +/- 22% (p = 0.027) of cells from BM. There was greater expansion of both total CD34(+) cells and the CD90(+) subset from MPB samples (p = 0.00 1 and 0.0001, respectively), Results from PHPs defined on the basis of AC13 3 expression correlated web with results obtained in CD90(+) subsets (r(2) = 0,81; p = 0.014). Conclusions. MPB PHPs appear to be primed for a greater acceleration in mit otic activity upon cytokine exposure. This qualitative difference may contr ibute to the earlier engraftment seen after HSCT using MPB grafts. (C) 2001 International Society for Experimental Hematology. Published by Elsevier S cience Inc.