Novel strategies for blood stem cell mobilization: special focus on plerixafor

Jantunen, Esa

doi:10.1517/14712598.2011.601737

Cited by 16 publications

(17 citation statements)

References 58 publications

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“…The reverse process during which HSCs cross the endothelial wall and the extracellular matrix barriers is similarly controlled (46,132,186,188,189,264,268,290,299,332,342,343). Knowledge of the molecular pathways governing the migration of HSCs has been translated to the clinic; innovative protocols for the harvest of large numbers of HSCs and the optimization of their engraftment after systemic infusion have been developed to enhance the success of bone marrow transplantation (5,121,150,219,220,268,287). In addition to HSCs, it has been recognized recently that the bone marrow serves as a reservoir for other types of stem and progenitors cells, including endothelial progenitor cells and mesenchymal stem cells (MSCs).…”

Section: Stem Cell Traffickingmentioning

confidence: 99%

Aging Effects on Cardiac Progenitor Cell Physiology

Rota

Goichberg

Anversa

et al. 2015

Comprehensive Physiology

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Cardiac aging has been confounded by the concept that the heart is a postmitotic organ characterized by a predetermined number of myocytes, which is established at birth and largely preserved throughout life until death of the organ and organism. Based on this premise, the age of cardiac cells should coincide with that of the organism; at any given time, the heart would be composed of a homogeneous population of myocytes of identical age. The discovery that stem cells reside in the heart and generate cardiac cell lineages has imposed a reconsideration of the mechanisms implicated in the manifestations of the aging myopathy. The progressive alterations of terminally differentiated myocytes, and vascular smooth muscle cells and endothelial cells may represent an epiphenomenon dictated by aging effects on cardiac progenitor cells (CPCs). Changes in the properties of CPCs with time may involve loss of self-renewing capacity, increased symmetric division with formation of daughter committed cells, partial depletion of the primitive pool, biased differentiation to the fibroblast fate, impaired ability to migrate, and forced entry into an irreversible quiescent state. Telomere shortening is a major variable of cellular senescence and organ aging, and support the notion that CPCs with critically shortened or dysfunctional telomeres contribute to myocardial aging and chronic heart failure. These defects constitute the critical variables that define the aging myopathy in humans. Importantly, a compartment of functionally competent human CPCs persists in the decompensated heart pointing to stem cell therapy as a novel form of treatment for the aging myopathy.

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Section: Stem Cell Traffickingmentioning

confidence: 99%

Aging Effects on Cardiac Progenitor Cell Physiology

Rota

Goichberg

Anversa

et al. 2015

Comprehensive Physiology

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“…The increase in PBSCs usually coincides with neutrophil recovery after the chemotherapy‐induced nadir. Mobilization with chemotherapy plus G‐CSF results in more CD34+ cells compared to G‐CSF alone but may have variability as to when CD34+ cell counts peak depending on which regimen is used, which makes it more difficult to predict when to initiate apheresis . The most commonly used chemotherapy regimens include cyclophosphamide at different doses, especially in patients with multiple myeloma (MM) .…”

Section: Historical Perspectivementioning

confidence: 99%

The evolving role of plerixafor in hematopoietic progenitor cell mobilization

Tanhehco¹,

Vogl²,

Stadtmauer³

et al. 2013

Transfusion

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The introduction of plerixafor as a peripheral blood stem cell mobilization agent has allowed more patients with multiple myeloma, non-Hodgkin's lymphoma, and Hodgkin's disease to mobilize sufficient hematopoietic progenitor cells (HPCs) to proceed to autologous transplantation. Because of the high cost of plerixafor, it is not routinely used in all patients undergoing HPC mobilization. If cost were not an issue, an argument could be made that plerixafor could be added to every mobilization regimen, but cost is an issue so in an attempt to be more cost-effective, many centers have limited plerixafor use to patients who have failed or who are predicted to fail collection of adequate numbers of cells by other methods. Additionally, plerixafor is now under investigation both for HPC collection of healthy donors for allogeneic stem cell transplantation and as an adjunct therapy (i.e., chemosensitizing agent) for acute leukemias. This article briefly reviews the role of plerixafor in autologous and allogeneic transplantation as well as its emerging role in the treatment of acute leukemias. Emphasis is placed on the choice of appropriate patients for plerixafor use to assure an adequate stem cell yield while maximizing the cost effectiveness of using plerixafor. The role of prophylactic collections and future areas of research are also presented.

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“…Although, the small molecule CXCR4 antagonist AMD3100 (Plerixafor) is used clinically in conjunction with granulocyte colony-stimulating factor (G-CSF) to improve harvesting of hematopoietic stem cells prior to autologous transplantation[45,46]. Furthermore, GSK812397[47], and AMD11070[48], have anti-HIV activity, the latter with clinical potential.…”

Section: Introductionmentioning

confidence: 99%

Discovery and Computer Aided Potency Optimization of a Novel Class of Small Molecule CXCR4 Antagonists

et al. 2013

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Amongst the chemokine signalling axes involved in cancer, chemokine CXCL12 acting on chemokine receptor CXCR4 is particularly significant since it orchestrates migration of cancer cells in a tissue-specific metastatic process. High CXCR4 tumour expression is associated with poor prognosis of lung, brain, CNS, blood and breast cancers. We have identified a new class of small molecule CXCR4 antagonists based on the use of computational modelling studies in concert with experimental determination of in vitro activity against CXCL12-induced intracellular calcium mobilisation, proliferation and chemotaxis. Molecular modelling proved to be a useful tool in rationalising our observed potencies, as well as informing the direction of the synthetic efforts aimed at producing more potent compounds.

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Novel strategies for blood stem cell mobilization: special focus on plerixafor

Cited by 16 publications

References 58 publications

Aging Effects on Cardiac Progenitor Cell Physiology

Aging Effects on Cardiac Progenitor Cell Physiology

The evolving role of plerixafor in hematopoietic progenitor cell mobilization

Discovery and Computer Aided Potency Optimization of a Novel Class of Small Molecule CXCR4 Antagonists

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