ArticleNeuropathology and applied neurobiology2019
A nonmyeloablative chimeric mouse model accurately defines microglia and macrophage contribution in glioma.
Article in Neuropathology and applied neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Chirality-Encoded Biomaterials Regulate Local and Systemic Immune Responses in Transplantation.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Plasma-to-tumour tissue integrated proteomics using nano-omics for biomarker discovery in glioblastoma.Nature communications · 2025Article
- Central IRF4/5 Signaling Are Critical for Microglial Activation and Impact on Stroke Outcomes.Translational stroke research · 2024Article
- Chimeric antigen receptor macrophages target and resorb amyloid plaques.JCI insight · 2024Article
- Interactions between microglia and glioma in tumor microenvironment.Frontiers in oncology · 2023Review
- Tumor Microenvironment and Immune Escape in the Time Course of Glioblastoma.Molecular neurobiology · 2022Article
- Signal Pathways Involved in the Interaction Between Tumor-Associated Macrophages/TAMs and Glioblastoma Cells.Frontiers in oncology · 2022Review
- Imaging of the glioma microenvironment by TSPO PET.European journal of nuclear medicine and molecular imaging · 2021Review
- ROS-Induced mtDNA Release: The Emerging Messenger for Communication between Neurons and Innate Immune Cells during Neurodegenerative Disorder Progression.Antioxidants (Basel, Switzerland) · 2021Review
- Constructing and programming a cost-effective murine running wheel with digital revolution counter.Lab animal · 2021Article
- Separated parabiont reveals the fate and lifespan of peripheral-derived immune cells in normal and ischaemia-induced injured kidneys.Open biology · 2021Article
- Microglia Diversity in Healthy and Diseased Brain: Insights from Single-Cell Omics.International journal of molecular sciences · 2021Review
- Cellular and Molecular Mechanisms Underlying Glioblastoma and Zebrafish Models for the Discovery of New Treatments.Cancers · 2021Review
- Distinction of Microglia and Macrophages in Glioblastoma: Close Relatives, Different Tasks?International journal of molecular sciences · 2020Review
- Distinct regional ontogeny and activation of tumor associated macrophages in human glioblastoma.Scientific reports · 2020Article
- Review
- Non-myeloablative busulfan chimeric mouse models are less pro-inflammatory than head-shielded irradiation for studying immune cell interactions in brain tumours.Journal of neuroinflammation · 2019Article
- A nonmyeloablative chimeric mouse model accurately defines microglia and macrophage contribution in glioma.Neuropathology and applied neurobiology · 2019Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsResident and peripherally derived glioma associated microglia/macrophages (GAMM) play a key role in driving tumour progression, angiogenesis, invasion and attenuating host immune responses. Differentiating these cells' origins is challenging and current preclinical models such as irradiation-based adoptive transfer, parabiosis and transgenic mice have limitations. We aimed to develop a novel nonmyeloablative transplantation (NMT) mouse model that permits high levels of peripheral chimerism without blood-brain barrier (BBB) damage or brain infiltration prior to tumour implantation.
methodsNMT dosing was determined in C57BL/6J or Pep3/CD45.1 mice conditioned with concentrations of busulfan ranging from 25 mg/kg to 125 mg/kg. Donor haematopoietic cells labelled with eGFP or CD45.2 were injected via tail vein. Donor chimerism was measured in peripheral blood, bone marrow and spleen using flow cytometry. BBB integrity was assessed with anti-IgG and anti-fibrinogen antibodies. Immunocompetent chimerised animals were orthotopically implanted with murine glioma GL-261 cells. Central and peripheral cell contributions were assessed using immunohistochemistry and flow cytometry. GAMM subpopulation analysis of peripheral cells was performed using Ly6C/MHCII/MerTK/CD64.
resultsNMT achieves >80% haematopoietic chimerism by 12 weeks without BBB damage and normal life span. Bone marrow derived cells (BMDC) and peripheral macrophages accounted for approximately 45% of the GAMM population in GL-261 implanted tumours. Existing markers such as CD45 high/low proved inaccurate to determine central and peripheral populations while Ly6C/MHCII/MerTK/CD64 reliably differentiated GAMM subpopulations in chimerised and unchimerised mice.
conclusionNMT is a powerful method for dissecting tumour microglia and macrophage subpopulations and can guide further investigation of BMDC subsets in glioma and neuro-inflammatory diseases.
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