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Related Concept Videos

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Generation of High-Throughput Three-Dimensional Tumor Spheroids for Drug Screening
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Tumoroid-On-a-Plate (ToP): Physiologically Relevant Cancer Model Generation and Therapeutic Screening.

Amir Seyfoori1,2,3, Kaiwen Liu2,3, Hector J Caruncho4

  • 1Department of Mechanical Engineering, University of Victoria, Victoria, BC, V8P 5C2, Canada.

Advanced Healthcare Materials
|November 14, 2024
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Summary

This study introduces the innovative Tumoroid-on-a-Plate (ToP) device, a 3D model that enhances cancer therapy research by mimicking tumor microenvironments for glioblastoma and pancreatic cancer. It aids in predicting drug responses and understanding cancer progression.

Keywords:
3D cell cultureco‐culturedrug screeningextracellular matrixreelintumoroid

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Area of Science:

  • Oncology
  • Biotechnology
  • Cancer Research

Background:

  • Three-dimensional (3D) in vitro models like organoids and spheroids are crucial for advancing cancer therapy research.
  • These models offer a more biologically relevant platform compared to traditional 2D cultures, bridging the gap to in vivo studies.
  • Understanding tumor microenvironments is key to developing effective, personalized cancer treatments.

Purpose of the Study:

  • To introduce and validate the Tumoroid-on-a-Plate (ToP) device, an open-surface microfluidic platform for creating predictive 3D solid tumor models.
  • To investigate the impact of extracellular matrix (ECM) composition on glioblastoma (GBM) invasiveness.
  • To evaluate the efficacy and toxicity of chemotherapeutics on 3D models of glioblastoma (GBM) and pancreatic adenocarcinoma (PDAC), including drug interactions.

Main Methods:

  • Development of the Tumoroid-on-a-Plate (ToP) device, integrating tumor cells, stromal cells, and ECM components.
  • Utilizing the ToP model to test varying GBM ECM compositions (e.g., collagen, reelin) to assess invasiveness.
  • Screening chemotherapeutics (temozolomide, iron-chelators) in single and binary combinations on ToP models of GBM and PDAC.
  • Co-culturing pancreatic adenocarcinoma (PDAC) tumoroids with human fibroblasts to study stromal influence.

Main Results:

  • The ToP device successfully replicates key aspects of glioblastoma (GBM) and pancreatic adenocarcinoma (PDAC) microenvironments.
  • Specific ECM components were shown to influence GBM invasiveness within the ToP model.
  • Chemotherapeutic screening revealed differential toxicity and apoptosis induction in GBM and PDAC tumoroids.
  • Co-culture experiments demonstrated that stromal fibroblasts enhance PDAC tumor growth and alter drug response.

Conclusions:

  • The Tumoroid-on-a-Plate (ToP) device represents a significant advancement in 3D in vitro cancer modeling.
  • This platform provides valuable insights into tumor progression, invasiveness, and drug response in complex microenvironments.
  • The ToP model holds promise for accelerating the development of more effective and personalized cancer therapies.