The phenotypic profile of CD34-positive peripheral blood stem cells in different mobilization regimens

Abstract

The type of regimen used might result in mobilization of phenotypically and functionally different CD34(+) cells. We compared the phenotype of CD34(+) cells in leukapheresis products of three homogeneous groups: I, healthy individuals treated with granulocyte colony-stimulating factor (G-CSF) alone (n = 13); II, patients mobilized with G-CSF following chemotherapy (n = 16); and III, patients mobilized with G-CSF after high-dose chemotherapeutic pretreatment (n = 24). Multiparameter flow cytometry was performed for CD34(+) subpopulation analysis and focused on adhesion molecules, differentiation markers and megakaryocytic markers relevant for stem cell homing, with special reference to the importance of L-selectin expression. Regimens I and II led to higher numbers of mobilized CD34(+) cells (mean 468 x 10(6) and 491 x 10(6) CD34(+) cells per leukapheresis procedure respectively) than regimen III (mean 41 x 10(6) CD34(+) cells per leukapheresis procedure). Both the expression of L-selectin and CD54 on CD34(+) cells was significantly lower in group III, as was the percentage of megakaryocytic (CD41(+)) progenitors. A higher percentage of primitive (CD38(-) and/or HLA(-)DR(-)) CD34(+) cells was found in group III, correlating with a higher clonogenicity of the CD34(+) cells. However, when comparing the CD34(+)_ subpopulations that were also positive for L-selectin, there was no significant difference between the three regimens. A similar approach for the megakaryocytic CD34+ population resulted in an even worse quality of regimen III: 5.1% of CD34(+) being CD41(+)/L-selectin(+) compared with 9.2% and 8.9% in regimens I and II respectively. We concluded that the phenotypes of the CD34(+) cells in the G-CSF (group I) and G-CSF-chemotherapy (group II) regimens are similar, whereas the phenotype of the CD34(+) cells mobilized in the high-dose regimen (group III) displayed features that might negatively influence homing of the cells. Future studies will be directed towards regimens that will lead to the mobilization of a higher amount of CD34(+) cells with a phenotypically favourable phenotype.

Improving stem cell mobilization strategies: future directions

“…38 However, there are conflicting reports on whether a mobilization regimen consisting of sequential administration of chemotherapy followed by G-CSF causes downregulation of these adhesion molecules. 38,118 Increases in matrix metalloproteinase-9 concentrations after mobilization with chemotherapy plus G-CSF have been noted to correlate with mobilization efficiency. 38 In addition, the toxicity of chemotherapeutic agents to the BM stroma could prompt the release of hematopoietic stem cells by damaging the functional ability of stromal cells to support stem cells.…”

Positive selection for CD90 as a purging option in acute myeloid leukemia stem cell transplants

“…Firstly, CD90 is a stem cell marker, expressed on 20-60% of normal CD34þ cells in mobilized PBSC transplants (6). It has been proven that CD34þCD90þ cells are able to provide hematopoietic reconstitution in vivo in animal models (7)(8)(9).…”

Bioequivalence of two recombinant granulocyte colony-stimulating factor formulations in healthy male volunteers

“…Increments in circulating leukocytes were exclusively due to ANC since other lineages did not have variations. The circulating CD34+ cell count increment has been suggested to be an adequate variable that measures stem cell mobilization [30][31][32][33]. The compared formulations did not differ significantly with respect to this variable either.…”