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Bioengineering Stem Cell-Derived Glioblastoma Organoids: A Comprehensive Review.

Alexandra D Avera1, Yonghyun Kim1

  • 1Department of Chemical and Biological Engineering, The University of Alabama, Tuscaloosa, AL 35487, USA.

Pharmaceuticals (Basel, Switzerland)
|December 31, 2025
PubMed
Summary

Glioblastoma organoids (GBOs) show promise for developing new treatments, but current manufacturing prioritizes convenience over biological accuracy, hindering clinical translation. Future GBOs need better defined components and larger sizes for improved relevance.

Keywords:
bioengineeringorganoidsstem cells

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Area of Science:

  • Biomedical Engineering
  • Cancer Research
  • Translational Medicine

Background:

  • Glioblastoma (GBM) is a fatal brain cancer with poor prognosis due to tumor heterogeneity and treatment resistance.
  • Current preclinical models inadequately represent GBM's complexity, limiting therapeutic development.
  • Organoids offer a more physiologically relevant in vitro model, but challenges remain in their biomanufacturing.

Purpose of the Study:

  • To review the advancements in glioblastoma organoid (GBO) biomanufacturing.
  • To analyze GBO development from an engineering perspective, focusing on the tumor microenvironment (TME).
  • To identify critical translational gaps and propose future directions for clinically relevant GBO models.

Main Methods:

  • Comprehensive literature review of GBO biomanufacturing over the last 15 years.
  • Analysis of GBM tumor microenvironment (TME) features.
  • Evaluation of GBO development through genetic, biochemical, biophysical, and process engineering lenses.

Main Results:

  • GBO biomanufacturing often prioritizes technical convenience over physiological relevance, impacting integrity and reproducibility.
  • Existing GBO models face limitations in maturity, vasculature, and immune cell integration.
  • Fundamental oversights in GBO development hinder their clinical applicability.

Conclusions:

  • The translational gap in GBOs stems from prioritizing ease of use over biological accuracy.
  • Future GBO development requires fully defined components, larger constructs for TME recapitulation, and enhanced functional readouts.
  • Improving GBOs is crucial for advancing novel therapeutics for glioblastoma.