Differential maturation of megakaryocyte progenitor cells from cord blood and mobilized peripheral blood

Schipper, Laurus F.; Brand, Anneke; Reniers, Nathalie; Melief, Cees J.J; Willemze, R.; Fibbe, Willem E.

doi:10.1016/s0301-472x(03)00004-3

Cited by 48 publications

(47 citation statements)

References 21 publications

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“…+ cells with TPO, the expression of CD61 (ITGB3, GPIIIa, or beta3 integrin), which forms part of the GPIIb/IIIa (CD41/CD61) complex that binds to vWF, fibronectin, fibrinogen, and vitronectin [40,43,51] + cells in the starting population. This double negative population has been shown to be responsible for the earlier platelet recovery in in vivo models [48].…”

Section: Culturing Cd34mentioning

confidence: 99%

“…+ cells for 7-9 days with TPO can lead to improved early platelet recovery in immune-deficient mice when compared to transplantation with untreated CB CD34 + cells in the single CB transplant setting, without apparently compromising longer term hematological reconstitution [42][43][44]. Since thrombocytopenia is a common complication of both single and dCB HSC transplants, it has been proposed from these studies that TPO treatment ex vivo of one or part of one CB unit in a dCB transplant setting might be especially useful in preventing delays in platelet recovery posttransplant and hence in improving the overall patient survival [1,45].…”

Section: Introductionmentioning

confidence: 99%

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Thrombopoietin Treatment of One Graft in a Double Cord Blood Transplant Provides Early Platelet Recovery While Contributing to Long-Term Engraftment in NSG Mice

Brand

et al. 2015

Stem Cells and Development

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Human cord blood (CB) hematopoietic stem cell (HSC) transplants demonstrate delayed early neutrophil and platelet recovery and delayed longer term immune reconstitution compared to bone marrow and mobilized peripheral blood transplants. Despite advances in enhancing early neutrophil engraftment, platelet recovery after CB transplantation is not significantly altered when compared to contemporaneous controls. Recent studies have identified a platelet-biased murine HSC subset, maintained by thrombopoietin (TPO), which has enhanced capacity for short-and long-term platelet reconstitution, can self-renew, and can give rise to myeloid-and lymphoidbiased HSCs. In previous studies, we have shown that transplantation of human CB CD34+ cells precultured in TPO as a single graft accelerates early platelet recovery as well as yielding long-term repopulation in immunedeficient mice. In this study, using a double CB murine transplant model, we investigated whether TPO cultured human CB CD34+ cells have a competitive advantage or disadvantage over untreated human CB CD34 + cells in terms of (1) short-term and longer term platelet recovery and (2) longer term hematological recovery. Our studies demonstrate that the TPO treated graft shows accelerated early platelet recovery without impairing the platelet engraftment of untreated CD34 + cells. Notably, this was followed by a dominant contribution to platelet production through the untreated CD34 + cell graft over the intermediate to longer term. Furthermore, although the contribution of the TPO treated graft to long-term hematological engraftment was reduced, the TPO treated and untreated grafts both contributed significantly to long-term chimerism in vivo.

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Section: Culturing Cd34mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Thrombopoietin Treatment of One Graft in a Double Cord Blood Transplant Provides Early Platelet Recovery While Contributing to Long-Term Engraftment in NSG Mice

Brand

et al. 2015

Stem Cells and Development

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“…Although they may provide a more definitive assessment of MK progenitor numbers, they are time-consuming, do not allow realtime evaluation and, since the colonies are the product of the proliferation of MK progenitors, they do not allow the analysis of the MK progenitor itself. However, MK progenitors can also be characterized by their expression of a range of cell surface markers, including CD41a and CD61 [13][14][15]. Such assessments can be performed rapidly and provide the potential for real-time assessment of MK progenitor cell numbers, prospective isolation, additional analyses, and therapeutic application.…”

Section: Introductionmentioning

confidence: 99%

Expression of a Surface Antigen (MA6) by Peripheral Blood CD34⁺Cells Is Correlated with Improved Platelet Engraftment and May Explain Delayed Platelet Engraftment Following Cord Blood Transplantation

Simmons

Robinson

Munsell

et al. 2015

Stem Cells and Development

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CD34 + cell dose provides a measure of hematopoietic tissue that predicts the rate of engraftment upon transplant. It is positively correlated with multiple measures of hematopoietic recovery, including platelet engraftment. Here we identify a subpopulation of CD34 + cells that coexpress a surface antigen-MA6, which is more positively correlated with platelet engraftment in a clinical setting than CD34 + alone. The specific identity and function of MA6 remain to be determined, however, it is expressed by primitive megakaryocyte (MK) progenitors, but is lost with differentiation and is not expressed by platelets. Commitment of CD34 + MA6 + cells to the MK lineage was confirmed by in vitro assays and their significance in hematopoietic transplantation explored by flow cytometric analysis of cryopreserved samples of granulocyte colony stimulating factor-mobilized peripheral blood progenitor cell (PBPC) products along with a retrospective analysis of platelet engraftment data. Platelet engraftment by day 21 was predicted by receipt of ‡ 6 · 10 6 CD34 + cells/kg or ‡ 0.3 · 10 6 CD34 + MA6 + cells/kg. Subsequent analysis of cord blood (CB) CD34 + cells revealed < 0.2% coexpressed MA6 + , compared to 8% of PBPC CD34 + cells. This low proportion of CD34 + MA6 + cells may be responsible, at least in part, for the delayed platelet engraftment associated with CB transplantation. However, platelet engraftment is markedly improved in recipients of ex vivo-expanded CB. This may be a consequence of an increased proportion of CD34 + MA6 + cells present in the ex vivo-expanded product and also suggests that optimizing ex vivo culture conditions to generate CD34 + MA6 + cells might further improve platelet engraftment in CB recipients.

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“…The kinetics of differentiation of CD34 ϩ cells was monitored at several intervals over 12 days by measuring the expression of the megakaryocytic markers GPIIb and GPIX. 15 Figure 1B illustrates the 2-color staining of GPIIb and GPIX expression on Mks as measured by flow cytometry. During the course of differentiation, cell-surface expression of GPIIb and GPIX was significant already on day 4 of culture with GPIIb at 85% Ϯ 15% and GPIX at 62% Ϯ 17% (n ϭ 3).…”

Section: Detection Of Mature Mks Derived From Human Cd34 ؉ Cells In Cmentioning

confidence: 99%

Quinine-induced thrombocytopenia: drug-dependent GPIb/IX antibodies inhibit megakaryocyte and proplatelet production in vitro

Perdomo

Feng

Ahmadi

et al. 2011

Blood

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Differential maturation of megakaryocyte progenitor cells from cord blood and mobilized peripheral blood

Cited by 48 publications

References 21 publications

Thrombopoietin Treatment of One Graft in a Double Cord Blood Transplant Provides Early Platelet Recovery While Contributing to Long-Term Engraftment in NSG Mice

Thrombopoietin Treatment of One Graft in a Double Cord Blood Transplant Provides Early Platelet Recovery While Contributing to Long-Term Engraftment in NSG Mice

Expression of a Surface Antigen (MA6) by Peripheral Blood CD34⁺Cells Is Correlated with Improved Platelet Engraftment and May Explain Delayed Platelet Engraftment Following Cord Blood Transplantation

Quinine-induced thrombocytopenia: drug-dependent GPIb/IX antibodies inhibit megakaryocyte and proplatelet production in vitro

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Differential maturation of megakaryocyte progenitor cells from cord blood and mobilized peripheral blood

Cited by 48 publications

References 21 publications

Thrombopoietin Treatment of One Graft in a Double Cord Blood Transplant Provides Early Platelet Recovery While Contributing to Long-Term Engraftment in NSG Mice

Thrombopoietin Treatment of One Graft in a Double Cord Blood Transplant Provides Early Platelet Recovery While Contributing to Long-Term Engraftment in NSG Mice

Expression of a Surface Antigen (MA6) by Peripheral Blood CD34+Cells Is Correlated with Improved Platelet Engraftment and May Explain Delayed Platelet Engraftment Following Cord Blood Transplantation

Quinine-induced thrombocytopenia: drug-dependent GPIb/IX antibodies inhibit megakaryocyte and proplatelet production in vitro

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Expression of a Surface Antigen (MA6) by Peripheral Blood CD34⁺Cells Is Correlated with Improved Platelet Engraftment and May Explain Delayed Platelet Engraftment Following Cord Blood Transplantation