The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on primitive hematopoietic stem cell (PHSC) function and numbers, after chemotherapy.

Gardner, Renee Vanessa; Begue, Rodolfo; McKinnon, Evangeline

doi:10.1016/s0301-472x(01)00685-3

Cited by 20Hematopoietic Stem Cell TransplantationBlood disorders and treatmentsMesenchymal stem cell research

The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on primitive hematopoietic stem cell (PHSC) function and numbers, after chemotherapy.

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Gardner, Renee Vanessa, Begue, Rodolfo, McKinnon, Evangeline·2001·Experimental Hematology

DOI 10.1016/s0301-472x(01)00685-3

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Abstract

Objective Primitive hematopoietic stem cell function was assessed after cyclophosphamide with granulocyte-macrophage colony-stimulating factor (GM-CSF), with or without preadministration of interleukin-1, using competitive repopulation.Methods C57B6/J mice injected with one or four biweekly intravenous injections of cyclophosphamide, 200 mg/kg, received granulocyte-macrophage colony-stimulating factor, 1 microg, subcutaneously for 5 days, beginning 24 hours after cyclophosphamide. Alternatively, mice were injected with interleukin-1, 1 microg, 20 hours before administration of drug or drug and cytokine. Marrow obtained from mice sacrificed 4 weeks after the last dose of drug or drug and cytokine was used in competitive repopulation.Results Significant reductions in marrow repopulating ability occurred after a single dose of cyclophosphamide or multiple injections. Repopulating units (RU) were calculated, and both binomial and Poisson models for estimation of primitive hematopoietic stem cell (PHSC) numbers were used. RU were significantly diminished for all treatment groups when compared to controls. PHSC numbers were not significantly affected by either regimen of cyclophosphamide given alone. Addition of GM-CSF to cyclophosphamide, whether the latter was given in single or multiple doses, led to further, although insignificant, declines in repopulating ability, as well as PHSC and RU numbers. Interleukin-1 usage exacerbated the observed repopulating defect. There was evidence of replicative failure in individual cells, indicating a qualitative defect also.Summary Additive stem cell depletion and qualitative replicative defect occur after chemotherapy-cytokine usage. However, the replicative defect of PHSC seen after addition of GM-CSF is not significantly worse than that seen with cytotoxic drug use alone.

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Some irradiated patients develop long-term or residual BM injuries manifested by decreases in HSC reserves and impairments in HSC self-renewal after recovering from IR-induced acute myelosuppression.
“However, some irradiated patients also develop long-term or residual BM injuries manifested by decreases in HSC reserves and impairments in HSC self-renewal after recovering from IR-induced acute myelosuppression.”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [4]
Residual BM damage is latent, long lasting, shows little tendency for recovery, and can lead to hypoplastic anemia or myelodysplastic syndrome at a later time or after additional hematopoietic stress.
“Although residual BM damage is latent, it is long lasting, shows little tendency for recovery, and can lead to the development of hypoplastic anemia or a myelodysplastic syndrome at a later time or after additional hematopoietic stress.4,5”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [4]

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Authors: Gardner, R. V., Begue, R., & McKinnon, E.
Affiliations: Louisiana State University Health Sciences Center New Orleans (US)
Venue: Experimental Hematology
Publisher: Elsevier BV
Published: 2001-09
Volume: 29
Issue: 9
Pages: 1053-1059
ISSN: 0301-472X (ISSN-L)
DOI: 10.1016/s0301-472x(01)00685-3
OpenAlex: W2093990209
Cited by: 20
References: 44
Citations by year: 2025: 2 · 2024: 1 · 2022: 1 · 2020: 1 · 2015: 2 · 2014: 1 · 2013: 2 · 2012: 1
FWCI: 0.49
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 7585 d)
Locations: Experimental Hematology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords: GM-CSF, cyclophosphamide, chemotherapy, interleukin-1, competitive repopulation, stem cell depletion, cytokine combination therapy
MeSH terms: Animals, Bone Marrow Cells, Cell Count, Cyclophosphamide, Drug Interactions, Drug Therapy, Combination, Hematopoiesis, Hematopoietic Stem Cells, Interleukin-1, Mice, Inbred C57BL, Granulocyte-Macrophage Colony-Stimulating Factor, Hematopoietic Stem Cell Transplantation, Antineoplastic Agents, Alkylating, Mice

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The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on primitive hematopoietic stem cell (PHSC) function and numbers, after chemotherapy.

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