Perivascular invasion of primary human glioblastoma cells in organotypic human brain slices: human cells migrating in human brain.


Journal

Journal of neuro-oncology
ISSN: 1573-7373
Titre abrégé: J Neurooncol
Pays: United States
ID NLM: 8309335

Informations de publication

Date de publication:
Aug 2023
Historique:
received: 20 04 2023
accepted: 18 05 2023
medline: 29 8 2023
pubmed: 25 7 2023
entrez: 25 7 2023
Statut: ppublish

Résumé

Glioblastoma (GBM) is an aggressive primary brain cancer. Lack of effective therapy is related to its highly invasive nature. GBM invasion has been studied with reductionist systems that do not fully recapitulate the cytoarchitecture of the brain. We describe a human-derived brain organotypic model to study the migratory properties of GBM IDH-wild type ex vivo. Non-tumor brain samples were obtained from patients undergoing surgery (n = 7). Organotypic brain slices were prepared, and green fluorescent protein (GFP)-labeled primary human GBM IDH-wild type cells (GBM276, GBM612, GBM965) were placed on the organotypic slice. Migration was evaluated via microscopy and immunohistochemistry. After placement, cells migrated towards blood vessels; initially migrating with limited directionality, sending processes in different directions, and increasing their speed upon contact with the vessel. Once merged, migration speed decreased and continued to decrease with time (p < 0.001). After perivascular localization, migration is limited along the blood vessels in both directions. The percentage of cells that contact blood vessels and then continue to migrate along the vessel was 92.5% (- 3.9/ + 2.9)% while the percentage of cells that migrate along the blood vessel and leave was 7.5% (- 2.9/ + 3.9) (95% CI, Clopper-Pearson (exact); n = 256 cells from six organotypic cultures); these percentages are significantly different from the random (50%) null hypothesis (z = 13.6; p < 10 Human organotypic models can accurately study cell migration ex vivo. GBM IDH-wild type cells migrate toward the perivascular space in blood vessels and their migratory parameters change once they contact vascular structures and under hypoxic conditions. This model allows the evaluation of GBM invasion, considering the human brain microenvironment when cells are removed from their native niche after surgery.

Identifiants

pubmed: 37490233
doi: 10.1007/s11060-023-04349-9
pii: 10.1007/s11060-023-04349-9
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

43-54

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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Auteurs

Rea Ravin (R)

Celoptics. Inc, Rockville, MD, USA.

Paola Suarez-Meade (P)

Department of Neurological Surgery, Mayo Clinic, Jacksonville, FL, USA.

Brad Busse (B)

Section On Integrative Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, 20892, USA.

Paul S Blank (PS)

Section On Integrative Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, 20892, USA.

Tito Vivas-Buitrago (T)

Department of Neurological Surgery, Mayo Clinic, Jacksonville, FL, USA.

Emily S Norton (ES)

Department of Neurological Surgery, Mayo Clinic, Jacksonville, FL, USA.
Neuroscience Program, Mayo Clinic Graduate School of Biomedical Sciences, Jacksonville, USA.
Regenerative Sciences Training Program, Mayo Clinic Graduate School of Biomedical Sciences, Jacksonville, USA.

Steve Graepel (S)

Department of Neurological Surgery, Mayo Clinic, Jacksonville, FL, USA.

Kaisorn L Chaichana (KL)

Department of Neurological Surgery, Mayo Clinic, Jacksonville, FL, USA.

Ludmila Bezrukov (L)

Section On Integrative Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, 20892, USA.

Hugo Guerrero-Cazares (H)

Department of Neurological Surgery, Mayo Clinic, Jacksonville, FL, USA.

Joshua Zimmerberg (J)

Section On Integrative Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, 20892, USA. zimmerberg.joshua@nih.gov.

Alfredo Quiñones-Hinojosa (A)

Department of Neurological Surgery, Mayo Clinic, Jacksonville, FL, USA. quinones@mayo.edu.
Brain Tumor Stem Cell Laboratory, Department of Neurologic Surgery Mayo Clinic, 4500 San Pablo Rd S, Jacksonville, FL, 32224, USA. quinones@mayo.edu.

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