The Advances in Glioblastoma On-a-Chip for Therapy Approaches

Abstract

This systematic review aimed to verify the use of microfluidic devices in the process of implementing and evaluating the effectiveness of therapeutic approaches in glioblastoma on-a-chip, providing a broad view of advances to date in the use of this technology and their perspectives. We searched studies with the variations of the keywords “Glioblastoma”, “microfluidic devices”, “organ-on-a-chip” and “therapy” of the last ten years in PubMed and Scopus databases. Of 446 articles identified, only 22 articles were selected for analysis according to the inclusion and exclusion criteria. The microfluidic devices were mainly produced by soft lithography technology, using the PDMS material (72%). In the microenvironment, the main extracellular matrix used was collagen type I. Most studies used U87-MG glioblastoma cells from humans and 31.8% were co-cultivated with HUVEC, hCMEC/D3, and astrocytes. Chemotherapy was the majority of therapeutic approaches, assessing mainly the cellular viability and proliferation. Furthermore, some alternative therapies were reported in a few studies (22.6%). This study identified a diversity of glioblastoma on-a-chip to assess therapeutic approaches, often using intermediate levels of complexity. The most advanced level implemented the intersection between different biological systems (liver–brain or intestine–liver–brain), BBB model, allowing in vitro studies with greater human genetic similarity, reproducibility, and low cost, in a highly customizable platform.

A Simple 3D Cell Culture Method for Studying the Interactions between Human Mesenchymal Stromal/Stem Cells and Patients Derived Glioblastoma

“…The protocol and culture conditions described herein have been made simple in order to provide an easy and reliable clinically relevant model, which could be used to design personalized treatments in the vast majority of GBM patients. This constitutes a basic prerequisite for the use of spheroids for the discovery of efficient therapies in this presently incurable tumor [29,30]. Of note, similar combinations of spheroids and TME cells in 3D conditions have been reported in many different cancers.…”

Scaffold‐based spheroid models of glioblastoma multiforme and its use in drug screening

“…This system evaluated the anti-invasion efficacy of resveratrol and TMZ individually and in combination with the GBM spheroids (Ma et al, 2018). This scalable model might be useful for identifying effective target specificity for treating extremely aggressive and organ-specific malignancies, which could lead to novel therapeutic options or even reveal optimum drug carrier combinations for targeted therapies (Alves et al, 2022;Piantino et al, 2021). Although GBM spheroids can be easily cultured in a scaffold-free system, it can be challenging to regulate their size and consistency.…”

Engineering the glioblastoma microenvironment with bioactive nanoparticles for effective immunotherapy

“…Most researchers utilize a human GBM cell line such as U87MG, with other studies also constructing co-cultures with HUVECs, astrocytes, or hCMEC/d3, a brain endothelial cell line. 141…”