The low cycling status of mobilized peripheral blood CD34+ cells is not restricted to the more primitive subfraction

Croockewit, Alexandra J.; Raymakers, R.A.P.; Smeets, M.E.P.; Bosch, G.; Pennings, A.H.M.; Witte, T De

doi:10.1038/sj.leu.2400981

Cited by 12 publications

(8 citation statements)

References 14 publications

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“…In accordance with previous studies, [18][19][20][21][22] it appears that the great majority of CD34 + cells from CB and particularly PB, are in G0/G1 phases of the cell cycle whereas more than 10% of the BM CD34 + cells are in S + G2M phases. We have also observed this difference between on the one hand, CB and PB and on the other hand, BM, for the immature CD34 + CD38…”

Section: Cd38supporting

confidence: 77%

Characterization of CD34+ subsets derived from bone marrow, umbilical cord blood and mobilized peripheral blood after stem cell factor and interleukin 3 stimulation

Bruyn

Delforge

Lagneaux

et al. 2000

Bone Marrow Transplant

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Section: Cd38supporting

confidence: 77%

Characterization of CD34+ subsets derived from bone marrow, umbilical cord blood and mobilized peripheral blood after stem cell factor and interleukin 3 stimulation

Bruyn

Delforge

Lagneaux

et al. 2000

Bone Marrow Transplant

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“…Besides the ease of collection, they initially appeared as optimal targets for retrovirus-mediated gene transfer, due to their cycling status, 11 a property that is necessary to ensure murine retrovirus integration into the host genome. 12 However, this early appreciation was recently reconsidered, with studies demonstrating that mobilized blood progenitors are actually low-cycling cells, 13,14 and that they however rapidly enter cell cycle when stimulated with cytokines. 15,16 Results of pre-clinical or clinical studies with genetically modified peripheral blood stem cells demonstrated that ex vivo retroviral gene transfer occurs.…”

Section: Introductionmentioning

confidence: 99%

Ex vivo manipulations alter the reconstitution potential of mobilized human CD34+ peripheral blood progenitors

Humeau

Namikawa²,

Bardin

et al. 1999

Leukemia

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The phenotype and functions of CD34؉ cells isolated from peripheral blood (PB) of steady-state healthy volunteers (ssPB-CD34), and of patients or healthy volunteers after mobilization (mPB-CD34) were investigated. ssPB-CD34؉ cells contain a lymphoid cell population that co-express T or B cell markers, while mPB-CD34 ؉ cells lack this population. After 5-day culture, significantly higher levels of expansion in cell, CD34؉ cell, and HPP-CFC numbers were induced in ssPB-CD34؉ cells, as compared to mPB-CD34 ؉ cells. Hematopoietic reconstitution potential of these ex vivo manipulated CD34؉ PBPC was evaluated in SCID-hu mice. It was found that ssPB-CD34؉ cells retained the potential to reconstitute human bone marrow (BM), as well as thymus implanted in SCID animals. In contrast, only very low levels of reconstitution were detected in human hematopoietic tissues injected with cultured mPB-CD34 ؉ cells. Reconstitution was restricted to myeloid cells, and no B cell reconstitution in bone marrow, or T cell reconstitution in thymus was achieved by these cells. The loss of B cell reconstitution potential of mPB-CD34؉ cells was shown to be induced in a time-dependent manner during culture. These results indicate that mPB-CD34؉ cells have different phenotypic and functional properties from ssPB-CD34 ؉ cells. This may affect the efficacy of cell and gene therapy with mobilized PBPC.

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“…One observed difference between the STRA cells in these two grafts from mobilized mice is the decreased proliferative activity of the progenitor cells in peripheral blood (Table 3). This phenotypical feature could explain the enhanced hematopoietic regeneration capacity of these peripheral blood cell grafts (16)(17)(18)(19)(20)(21)(22). Indeed, we found a correlation between the proliferative activity of the STRA cells and the hematopoietic regeneration, i.e., grafts consisting of quiescent stem cells (i.e., peripheral blood cells), engraft better than those grafts containing active proliferating progenitors (i.e., bone marrow cells) (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…It is reported that the cell cycle status of the stem cell subsets might have an impact on the engraftment capacity (16)(17)(18)(19)(20)(21)(22). These findings prompted us to investigate the effects of a mobilization protocol-cyclophosphamide (CTX) in combination with granulocyte colony-stimulating factor (G-CSF)-on the proliferative activity of the progenitor subsets and on the repopulation kinetics of mobilized PBSCs versus bone marrow cells in mice.…”

Section: Introductionmentioning

confidence: 99%

Peripheral Blood Stem Cells Differ from Bone Marrow Stem Cells in Cell Cycle Status, Repopulating Potential, and Sensitivity Toward Hyperthermic Purging in Mice Mobilized with Cyclophosphamide and Granulocyte Colony-Stimulating Factor

Wierenga

Setroikromo

Kamps

et al. 2002

Journal of Hematotherapy & Stem Cell Research

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Peripheral blood stem cells (PBSCs) are increasingly used in autologous stem cell transplantations. We investigated the mobilizing effect of a combined cyclophosphamide (CTX) and granulocyte colony-stimulating factor (G-CSF) treatment on progenitor cells (STRA) and primitive stem cells (LTRA) in normal and splenectomized CBA/H mice. This combined treatment not only resulted in mobilization but also in expansion of hematopoietic stem cell subsets. The latter phenomenon was somewhat suppressed in splenectomized animals, but in these mice an enhanced mobilization of STRA and LTRA cells into the peripheral blood was observed. Furthermore, we studied the engraftment potential of mobilized PBSCs. Mice transplanted with PBSCs engrafted significantly better compared to mice transplanted with bone marrow stem cells from control and mobilized mice. The repopulation curve was characterized by a less-deep nadir indicating that the differences occur during the initial phase after transplantation. Contamination of autologous PBSC transplants with malignant cells is noticed frequently and is the basis for urging the use of purging modalities. Here we used hyperthermia and found that the mobilized progenitor cells in peripheral blood are more resistant to hyperthermia than those in the bone marrow (i.e., a survival of 11 +/- 5% after 90 min at 43 degrees C for peripheral blood progenitors, compared to 0.5 +/- 0.4% in bone marrow of mobilized animals and 1.6 +/- 0.5% in normal animals, respectively). Hyperthermic purging does not eliminate the superior repopulating features of a PBSC graft, as is demonstrated by an increased median survival time of lethally irradiated mice transplanted with purged PBSCs. In conclusion, our data demonstrate that CTX + G-CSF-mobilized PBSCs have an enhanced engraftment potential concomitantly with a decreased cycling activity and hence a decreased hyperthermic sensitivity. These findings support the use of these mobilized PBSCs for autologous stem cell transplantation and strengthen the basis for using hyperthermia as a purging modality.

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The low cycling status of mobilized peripheral blood CD34+ cells is not restricted to the more primitive subfraction

Cited by 12 publications

References 14 publications

Characterization of CD34+ subsets derived from bone marrow, umbilical cord blood and mobilized peripheral blood after stem cell factor and interleukin 3 stimulation

Characterization of CD34+ subsets derived from bone marrow, umbilical cord blood and mobilized peripheral blood after stem cell factor and interleukin 3 stimulation

Ex vivo manipulations alter the reconstitution potential of mobilized human CD34+ peripheral blood progenitors

Peripheral Blood Stem Cells Differ from Bone Marrow Stem Cells in Cell Cycle Status, Repopulating Potential, and Sensitivity Toward Hyperthermic Purging in Mice Mobilized with Cyclophosphamide and Granulocyte Colony-Stimulating Factor

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