Visualization of spatiotemporal dynamics of human glioma stem cell invasion

Molecular Brain

Raita Fukaya¹  Kazunari Yoshida²  Yukina Morimoto²  Ryota Tamura²  Masahiro Toda²  Hirotaka Masuda³  Tetsuo Maruyama³  Minoru Narita⁴  Chizuru Iwasawa⁴  Hideyuki Okano⁵  Hiroyuki Miyoshi⁵  Munehisa Shinozaki⁵  Yutaka Mine⁵  Hideyuki Saya⁶  Oltea Sampetrean⁶ 

[1] Department of Neurosurgery, Fuji Hospital;Department of Neurosurgery, Keio University School of Medicine;Department of Obstetrics and Gynecology, Keio University School of Medicine;Department of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical Sciences;Department of Physiology, Keio University School of Medicine;Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine;

关键词: Glioblastoma;    Glioma stem cell;    Invasion;    Brain slice culture;    Time-lapse imaging;    Tissue clearing;   

DOI  :  10.1186/s13041-019-0462-3

来源: DOAJ

【 摘 要 】

Abstract Glioblastoma exhibits phenotypic and genetic heterogeneity, aggressive invasiveness, therapeutic resistance, and tumor recurrence, which can be explained by the existence of glioma stem cells (GSCs). In this study, we visualized the spatiotemporal dynamics of invasion of human GSCs in an orthotopic xenograft mouse model using time-lapse imaging of organotypic brain slice cultures and three-dimensional imaging of optically cleared whole brains. GSCs implanted in the striatum exhibited directional migration toward axon bundles, perivascular area, and the subventricular zone around the inferior horn of the lateral ventricle. GSCs migrated in a helical pattern around axon bundles in the striatum and invaded broadly in both the rostral and caudal directions. GSCs in the corpus callosum migrated more rapidly and unidirectionally toward the contralateral side with pseudopod extension. These characteristics of GSC invasion shared histological features observed in glioblastoma patients. Spatiotemporal visualization techniques can contribute to the elucidation of the mechanisms underlying GSC invasion that may lead to the development of effective therapy for glioblastoma.

【 授权许可】

Unknown