論文

査読有り
2021年1月

Mesenchymal glioblastoma-induced mature de-novo vessel formation of vascular endothelial cells in a microfluidic device

Molecular Biology Reports
  • Takeo Amemiya
  • Nobuhiro Hata
  • Masahiro Mizoguchi
  • Ryuji Yokokawa
  • Yoichiro Kawamura
  • Ryusuke Hatae
  • Yuhei Sangatsuda
  • Daisuke Kuga
  • Yutaka Fujioka
  • Kosuke Takigawa
  • Yojiro Akagi
  • Koji Yoshimoto
  • Koji Iihara
  • Takashi Miura
  • 全て表示

48
1
開始ページ
395
終了ページ
403
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s11033-020-06061-7
出版者・発行元
Springer Science and Business Media LLC

<title>Abstract</title>High vascularization is a biological characteristic of glioblastoma (GBM); however, an <italic>in-vitro</italic> experimental model to verify the mechanism and physiological role of vasculogenesis in GBM is not well-established. Recently, we established a self-organizing vasculogenic model using human umbilical vein endothelial cells (HUVECs) co-cultivated with human lung fibroblasts (hLFs). Here, we exploited this system to establish a realistic model of vasculogenesis in GBM. We developed two polydimethylsiloxane (PDMS) devices, a doughnut-hole dish and a 5-lane microfluidic device to observe the contact-independent effects of glioblastoma cells on HUVECs. We tested five patient-derived and five widely used GBM cell lines. Confocal fluorescence microscopy was used to observe the morphological changes in Red Fluorescent Protein (RFP)-HUVECs and fluorescein isothiocyanate (FITC)-dextran perfusion. The genetic and expression properties of GBM cell lines were analyzed. The doughnut-hole dish assay revealed KNS1451 as the only cells to induce HUVEC transformation to vessel-like structures, similar to hLFs. The 5-lane device assay demonstrated that KNS1451 promoted the formation of a vascular network that was fully perfused, revealing the functioning luminal construction. Microarray analysis revealed that KNS1451 is a mesenchymal subtype of GBM. Using a patient-derived mesenchymal GBM cell line, mature <italic>de-novo</italic> vessel formation could be induced in HUVECs by contact-independent co-culture with GBM in a microfluidic device. These results support the development of a novel in vitro research model and provide novel insights in the neovasculogenic mechanism of GBM and may potentially facilitate the future detection of unknown molecular targets.

リンク情報
DOI
https://doi.org/10.1007/s11033-020-06061-7
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000604190000004&DestApp=WOS_CPL
URL
http://link.springer.com/content/pdf/10.1007/s11033-020-06061-7.pdf
URL
http://link.springer.com/article/10.1007/s11033-020-06061-7/fulltext.html
ID情報
  • DOI : 10.1007/s11033-020-06061-7
  • ISSN : 0301-4851
  • eISSN : 1573-4978
  • Web of Science ID : WOS:000604190000004

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