Vascularized cancer on a chip: The effect of perfusion on growth and drug delivery of tumor spheroid

Yuji Nashimoto, Ryu Okada, Sanshiro Hanada, Yuichiro Arima, Koichi Nishiyama, Takashi Miura, Ryuji Yokokawa

Research output: Contribution to journalArticle

Abstract

Tumor vasculature creates a hostile tumor microenvironment (TME) in vivo and nourishes cancers, resulting in cancer progression and drug resistance. To mimic the biochemical and biomechanical environments of tumors in vitro, several models integrated with a vascular network have been reported. However, the tumor responses to biochemical and biomechanical stimuli were evaluated under static conditions and failed to incorporate the effects of blood flow to tumors. In this study, we present a tumor-on-a-chip platform that enables the evaluation of tumor activities with intraluminal flow in an engineered tumor vascular network. The fibroblasts in the tumor spheroid induced angiogenic sprouts, which constructed a perfusable vascular network in a tumor spheroid. The perfusability of the engineered vascular network was preserved during the culture. Moreover, perfusion for over 24 h significantly increased the proliferation activities of tumor cells and decreased cell death in the spheroid. Drug administration under perfusion condition did not show the dose-dependent effects of anticancer drugs on tumor activities in contrast to the results under static conditions. Our results demonstrate the importance of flow in a vascular network for the evaluation of tumor activities in a drug screening platform.

Original languageEnglish
Article number119547
JournalBiomaterials
Volume229
DOIs
Publication statusPublished - Jan 2020

Fingerprint

Drug delivery
Tumors
Perfusion
Growth
Pharmaceutical Preparations
Neoplasms
Blood Vessels
Preclinical Drug Evaluations
Tumor Microenvironment
Cell death
Fibroblasts
Drug Resistance
Screening
Blood
Cell Death
Cells

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Vascularized cancer on a chip : The effect of perfusion on growth and drug delivery of tumor spheroid. / Nashimoto, Yuji; Okada, Ryu; Hanada, Sanshiro; Arima, Yuichiro; Nishiyama, Koichi; Miura, Takashi; Yokokawa, Ryuji.

In: Biomaterials, Vol. 229, 119547, 01.2020.

Research output: Contribution to journalArticle

Nashimoto, Yuji ; Okada, Ryu ; Hanada, Sanshiro ; Arima, Yuichiro ; Nishiyama, Koichi ; Miura, Takashi ; Yokokawa, Ryuji. / Vascularized cancer on a chip : The effect of perfusion on growth and drug delivery of tumor spheroid. In: Biomaterials. 2020 ; Vol. 229.
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