CD34+ cells obtained from "good mobilizers" are more activated and exhibit lower ex vivo expansion efficiency than their counterparts from "poor mobilizers".
BACKGROUND
The classification of patients into "good" or "poor" mobilizers is based on CD34+ cell count in their peripheral blood (PB) after granulocyte-colony-stimulating factor (G-CSF) injection. We hypothesized that, apart from their mobilization from marrow to the blood, the response to G-CSF of CD34+ cells also includes activation of proliferation, metabolic activity, and proliferative capacity.


METHODS
Mobilized PB CD34+ cells purified from samples obtained by cytapheresis of multiple myeloma or non-Hodgkin's lymphoma patients of both good (>50 CD34+ cells/microL) and poor (< or =50 CD34+ cells/microL) mobilizers were studied. The initial cell cycle state of CD34+ cells after selection and their kinetics of activation (exit from G(0) phase) during ex vivo culture were analyzed. Their proliferative capacity was estimated on the basis of ex vivo generation of total cells, CD34+ cells, and colony-forming cells (CFCs), in a standardized expansion culture. Indirect insight in metabolic activity was obtained on the basis of their survival (viability and apoptosis follow-up) during the 7-day-long conservation in hypothermia (4 degrees C) in the air or in atmosphere containing 3% O(2)/6% CO(2).


RESULTS
CD34+ cells obtained from good mobilizers were in lower proportion in the G(0) phase, their activation in a cytokine-stimulated culture was accelerated, and they exhibited a lower ex vivo expansion efficiency than those from poor mobilizers. The resistance to hypothermia of good immobilizers' CD34+ cells is impaired.


CONCLUSIONS
A good response to G-CSF mobilization treatment is associated with a higher degree of proliferative and metabolic activation of mobilized CD34+ cells with a decrease in their expansion capacity.
Ivanovic
Zoran
Z
Aquitaine-Limousin Branch of French Blood Institute and the University Victor Segalen Bordeaux 2, Bordeaux, France. zoran.ivanovic@efs.sante.fr
Kovacevic-Filipovic
Milica
M
Jeanne
Michel
M
Ardilouze
Leslie
L
Bertot
Anne
A
Szyporta
Milène
M
Hermitte
Francis
F
Lafarge
Xavier
X
Duchez
Pascale
P
Vlaski
Marija
M
Milpied
Noel
N
Pavlovic
Mirjana
M
Praloran
Vincent
V
Boiron
Jean-Michel
JM
D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D002245:Carbon Dioxide / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D015925:Cryopreservation; D004734:Energy Metabolism / Q000502:physiology*; D016193:G1 Phase / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D010100:Oxygen / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000502:physiology
D018952:Antigens, CD34; D002245:Carbon Dioxide; D016179:Granulocyte Colony-Stimulating Factor; D010100:Oxygen