Chimeric Mouse model to track the migration of bone marrow derived cells in glioblastoma following anti-angiogenic treatments

Cancer Biology & Therapy
B R AchyutAli S Arbab

Abstract

Bone marrow derived cells (BMDCs) have been shown to contribute in the tumor development. In vivo animal models to investigate the role of BMDCs in tumor development are poorly explored. We established a novel chimeric mouse model using as low as 5 × 10(6) GFP+ BM cells in athymic nude mice, which resulted in >70% engraftment within 14 d. In addition, chimera was established in NOD-SCID mice, which displayed >70% with in 28 d. Since anti-angiogenic therapies (AAT) were used as an adjuvant against VEGF-VEGFR pathway to normalize blood vessels in glioblastoma (GBM), which resulted into marked hypoxia and recruited BMDCs to the tumor microenvironment (TME). We exploited chimeric mice in athymic nude background to develop orthotopic U251 tumor and tested receptor tyrosine kinase inhibitors and CXCR4 antagonist against GBM. We were able to track GFP+ BMDCs in the tumor brain using highly sensitive multispectral optical imaging instrument. Increased tumor growth associated with the infiltration of GFP+ BMDCs acquiring suppressive myeloid and endothelial phenotypes was seen in TME following treatments. Immunofluorescence study showed GFP+ cells accumulated at the site of VEGF, SDF1 and PDGF expression, and at the periphery of the tumo...Continue Reading

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Citations

Mar 28, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Molly BraunKrishnan M Dhandapani
Dec 21, 2017·International Journal of Molecular Sciences·Ali S ArbabBhagelu R Achyut
Oct 25, 2017·Scientific Reports·B R AchyutAli S Arbab
Jul 3, 2021·Cancers·Ruth M UrbantatSusan Brandenburg

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Methods Mentioned

BETA
biopsy
transgenic
xenograft
flow cytometry
flowcytometry

Software Mentioned

BD Accuri C6
Carestream
ImageJ
AMI view

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