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Cited by 35Glioma Diagnosis and TreatmentMesenchymal stem cell researchNanoparticle-Based Drug Delivery

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Human mesenchymal stromal cells as cellular drug-delivery vectors for glioblastoma therapy: a good deal?

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Clavreul, Anne, Pourbaghi-Masouleh, Milad, Roger, Emilie, Lautram, Nolwenn, Montero-Menei, Claudia N., Menei, Philippe·2017·Journal of Experimental & Clinical Cancer Research
DOI 10.1186/s13046-017-0605-2PMC PMC5622550
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Abstract

BACKGROUND: Glioblastoma (GB) is the most malignant brain tumor in adults. It is characterized by angiogenesis and a high proliferative and invasive capacity. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) is of limited efficacy. Innovative anticancer drugs targeting both tumor cells and angiogenesis are urgently required, together with effective systems for their delivery to the brain. We assessed the ability of human mesenchymal stromal cells (MSCs) to uptake the multikinase inhibitor, sorafenib (SFN), and to carry this drug to a brain tumor following intranasal administration. METHOD: MSCs were primed with SFN and drug content and release were quantified by analytical chemistry techniques. The ability of SFN-primed MSCs to inhibit the survival of the human U87MG GB cell line and endothelial cells was assessed in in vitro assays. These cells were then administered intranasally to nude mice bearing intracerebral U87MG xenografts. Their effect on tumor growth and angiogenesis was evaluated by magnetic resonance imaging and immunofluorescence analyses, and was compared with the intranasal administration of unprimed MSCs or SFN alone. RESULTS: MSCs took up about 9 pg SFN per cell, with no effect on viability, and were able to release 60% of the primed drug. The cytostatic activity of the released SFN was entirely conserved, resulting in a significant inhibition of U87MG and endothelial cell survival in vitro. Two intranasal administrations of SFN-primed MSCs in U87MG-bearing mice resulted in lower levels of tumor angiogenesis than the injection of unprimed MSCs or SFN alone, but had no effect on tumor volume. We also observed an increase in the proportion of small intratumoral vessels in animals treated with unprimed MSCs; this effect being abolished if the MSCs were primed with SFN. CONCLUSION: We show the potential of MSCs to carry SFN to brain tumors following an intranasal administration. However, the therapeutic effect is modest probably due to the pro-tumorigenic properties of MSCs, which may limit the action of the released SFN. This calls into question the suitability of MSCs for use in GB therapy and renders it necessary to find methods guaranteeing the safety of this cellular vector after drug delivery.

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References 64 · Cited by 35

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Metadata

Authors
Clavreul, A., Pourbaghi-Masouleh, M., Roger, E., Lautram, N., Montero-Menei, C. N., & Menei, P.
Affiliations
  • Inserm (FR)
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
Clavreul, Anne
ORCID
Venue
Journal of Experimental & Clinical Cancer Research
Publisher
Springer Science and Business Media LLC
Published
2017-09-29
Volume
36
Issue
1
Pages
135-135
ISSN
  • 0392-9078 (ISSN-L)
  • 1756-9966
DOI
10.1186/s13046-017-0605-2
PMC
PMC5622550
OpenAlex
W2757665254
Cited by
35
References
64
Citations by year
2025: 3 · 2024: 4 · 2023: 5 · 2022: 5 · 2021: 5 · 2020: 7 · 2019: 1 · 2018: 5
FWCI
2.04
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Journal of Experimental & Clinical Cancer Research (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • University of Miami
  • European Commission
  • Institut National de la Santé et de la Recherche Médicale
  • Ligue Contre le Cancer
  • Fondation de France
  • Education, Audiovisual and Culture Executive Agency
Topics
  • Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
glioblastoma, mesenchymal stem cells, sorafenib, intranasal administration, tumor angiogenesis, U87MG xenograft, multikinase inhibitor, brain tumor therapy
MeSH terms
Sorafenib, Administration, Intranasal, Animals, Antineoplastic Agents, Brain Neoplasms, Cell Survival, Glioblastoma, Humans, Mice, Nude, Niacinamide, Phenylurea Compounds, Treatment Outcome, Xenograft Model Antitumor Assays, Mesenchymal Stem Cell Transplantation, Cell Line, Tumor, Cell Proliferation, Mice, Mesenchymal Stem Cells

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