VARIATION IN CELL YIELD AND PROLIFERATIVE ACTIVITY OF POSITIVE SELECTED HUMAN CD34(-MARROW CELLS ALONG THE CIRCADIAN TIME-SCALE() BONE)

Variations in cell yield and proliferative activity of human bone marr ow (BM) progenitor cells were determined with flow cytometry along the 24-h (circadian) time scale. Equal volumes of BM were aspirated every 5 h, altogether 5 times in 5 healthy men. An average 6-fold higher yi eld of positive selected CD34(+) cells occurred in each subject when B M was aspirated during the daytime and late afternoon, while a lower y ield occurred during the night. Using all CD34(+) cell yield data norm alized to percentage of mean, a significant time-effect was found by A NOVA (p=0.02) and a significant circadian rhythm was detected by the l east-squares fit of a 24 h cosine (p=0.02). The 95% confidence limits of the acrophase (time of highest values) were computed to be at midda y between 10:24 and 14:48 h. A highly significant correlation (p=0.001 ) was found between proliferation of positive selected CD34(+) cells a nd the more mature myeloid precursor cells from the same BM aspirates, suggesting a common temporal pattern along the circadian time scale. However, no correlation was demonstrated between proliferation and cel l yield of CD34(+) selected cells, suggesting that mechanisms other th an variation in proliferation may cause the circadian rhythm in stem c ell yield. These circadian variations in stem cell yield and prolifera tion suggest that proper timing within 24 h may potentially be importa nt regarding outcome from progenitor cell harvesting and treatment wit h haematopoietic growth factors.