Efficient mobilization of haematopoietic progenitors after a single injection of pegylated recombinant human granulocyte colony‐stimulating factor in mouse strains with distinct marrow‐cell pool sizes

Haan, Gerald de; Ausema, Albertina; Wilkens, Marga; Molineux, Graham; Dontje, Bert

doi:10.1046/j.1365-2141.2000.02252.x

Cited by 48 publications

(27 citation statements)

References 35 publications

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“…PEGylated molecules are characterized by a prolonged elimination (Tb) half-life and sustained biological activity compared to their non-PEGylated counterparts. [42][43][44][45][46][47] This pattern of bioactivity is similar to our results with the PG-Flt3L sustained-release formulation, although, as discussed above, the PG formulation also augments and accelerates hematopoietic activity, unlike PEGylation.…”

Section: Discussionsupporting

confidence: 76%

Delivery of Flt3 ligand (Flt3L) using a poloxamer-based formulation increases biological activity in mice

Robinson

Chavez

Писарев

et al. 2003

Bone Marrow Transplant

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Summary:Fms-like tyrosine kinase (Flt3L) is a potent stimulator of hematopoietic progenitor cell (HPC) expansion and mobilization; however, this requires 7-10 days of administration. We investigated whether sustained delivery of Flt3L using a poloxamer-based matrix (PG) could accelerate and/or improve the hematopoietic activity of Flt3L in mice. A single injection of PG-Flt3L stimulated significantly more rapid and greater HPC mobilization to the spleen and peripheral blood than the daily injection of Flt3L formulated in saline. Pharmacokinetic analysis demonstrated that the formulation of Flt3L in PG prolonged its elimination (Tb) half-life (2.3-fold) and increased its bioavailability (4two fold) and the time to maximum serum concentration (T max ) (2.7-fold). Further, coadministration of G-CSF and PG-Flt3L allowed lower doses of Flt3L to be active, with significantly greater hematopoietic and mobilization activity, compared to the same total dose of G-CSF, Flt3L or G-CSF and Flt3L formulated in saline. These data demonstrate that formulation of Flt3L in PG significantly accelerates and increases HPC expansion and mobilization. The observation of increased bioactivity by PG-Flt3L in rodents suggests the potential for improved clinical efficacy of Flt3L by reducing the time required for HPC mobilization.

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Section: Discussionsupporting

confidence: 76%

Delivery of Flt3 ligand (Flt3L) using a poloxamer-based formulation increases biological activity in mice

Robinson

Chavez

Писарев

et al. 2003

Bone Marrow Transplant

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“…This was done to investigate whether PEGF administration in our conditions recapitulates described effects [19] in vivo on the HSC population. Blood samples were obtained before the onset of the treatment (10 weeks) and 4 days after each PEGF administration, when the approximate peak of mobilization can be estimated to occur [36]. At each age, the results were expressed as fold change of the basal percentage of each cell type in PEGF-mobilized animals compared with vehicle controls (fig.…”

Section: Resultsmentioning

confidence: 99%

Granulocyte Colony-Stimulating Factor Ameliorates Skeletal Muscle Dysfunction in Amyotrophic Lateral Sclerosis Mice and Improves Proliferation of SOD1-G93A Myoblasts in vitro

Rando¹,

Gasco²,

Torre³

et al. 2016

Neurodegener Dis

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Background: Amyotrophic lateral sclerosis (ALS) causes loss of upper and lower motor neurons as well as skeletal muscle (SKM) dysfunction and atrophy. SKM is one of the tissues involved in the development of ALS pathology, and studies in a SOD1-G93A mouse model of ALS have demonstrated alterations in SKM degeneration/regeneration marker expression in vivo and defective mutant myoblast proliferation in vitro. Granulocyte colony-stimulating factor (G-CSF) has been shown to alleviate SOD1-G93A pathology. However, it is unknown whether G-CSF may have a direct effect on SKM or derived myoblasts. Objective: To investigate effects of G-CSF and its analog pegfilgrastim (PEGF) on SOD1-G93A- associated SKM markers in vivo and those of G-CSF on myoblast proliferation in vitro. Methods: The effect of PEGF treatment on hematopoietic stem cell mobilization, survival, and motor function was determined. RNA expression of SKM markers associated with mutant SOD1 expression was quantified in response to PEGF treatment in vivo, and the effect of G-CSF on the proliferation of myoblasts derived from mutant and control muscles was determined in vitro. Results: Positive effects of PEGF on hematopoietic stem cell mobilization, survival, and functional assays in SOD1-G93A animals were confirmed. In vivo PEGF treatment augmented the expression of its receptor Csf3r and alleviated typical markers for mutant SOD1 muscle. Additionally, G-CSF was found to directly increase the proliferation of SOD1-G93A, but not wild-type primary myoblasts in vitro. Conclusion: Our results support the beneficial role of the G-CSF analog PEGF in a SOD1-G93A model of ALS. Thus, G-CSF andits analogs may be directly beneficial in diseases where the SKM function is compromised.

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“…In addition, the absolute number and proliferative capacity of HSCs in C57BL/6J mice is comparatively lower than that of "good mobilizer" mouse strains (42). Thus we chose C57BL/6J as a model of "poor mobilizers," to investigate the potential for the combination treatment of retinoids plus G-CSF to enhance mobilization of HSPC.…”

Section: Resultsmentioning

confidence: 98%

Granulocyte Colony-Stimulating Factor and an RAR?? Specific Agonist, VTP195183, Synergize to Enhance the Mobilization of Hematopoietic Progenitor Cells

Herbert

Walkley²,

Winkler³

et al. 2007

Transplantation

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VTP195183 treatment increases the numbers of immature granulocyte progenitors in BM and subsequently synergizes to enhance G-CSF-mediated mobilization of HSPC. These data demonstrate a novel approach to improve G-CSF-induced mobilization by accelerating granulocyte maturation in the BM. These findings are currently being tested in a clinical trial of VTP195183 plus G-CSF for mobilization of HSPC in human patients.

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Efficient mobilization of haematopoietic progenitors after a single injection of pegylated recombinant human granulocyte colony‐stimulating factor in mouse strains with distinct marrow‐cell pool sizes

Cited by 48 publications

References 35 publications

Delivery of Flt3 ligand (Flt3L) using a poloxamer-based formulation increases biological activity in mice

Delivery of Flt3 ligand (Flt3L) using a poloxamer-based formulation increases biological activity in mice

Granulocyte Colony-Stimulating Factor Ameliorates Skeletal Muscle Dysfunction in Amyotrophic Lateral Sclerosis Mice and Improves Proliferation of SOD1-G93A Myoblasts in vitro

Granulocyte Colony-Stimulating Factor and an RAR?? Specific Agonist, VTP195183, Synergize to Enhance the Mobilization of Hematopoietic Progenitor Cells

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