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Generation of Advanced Blood-Brain Barrier Spheroids Using Human-Induced Pluripotent Stem Cell-Derived Brain
Sanjana Mathew-Schmitt1, Sabrina Oerter1,2, Evelin Reitenbach2
1Chair Tissue Engineering and Regenerative Medicine (TERM), University Hospital Würzburg, 97070, Würzburg, Germany.
Advanced Biology
|February 6, 2025
Summary
This study introduces a 3D blood-brain barrier (BBB) spheroid model using human cells, offering a more accurate in-vitro system than traditional 2D models for drug development.
Area of Science:
- Neuroscience
- Biotechnology
- Cell Biology
Background:
- Traditional 2D cell culture inserts for blood-brain barrier (BBB) models lack in-vivo microenvironment accuracy due to limited neurovascular unit cellular contact.
- Accurate in-vitro BBB models are crucial for understanding neurological diseases and developing targeted therapies.
Purpose of the Study:
- To establish and characterize a self-assembled 3D BBB spheroid model using human-induced pluripotent stem cell (hiPSC)-derived brain capillary endothelial-like cells (iBCECs), primary human astrocytes (ACs), and pericytes (PCs).
- To compare the 3D spheroid model with conventional 2D BBB models derived from different hiPSC lines and differentiation strategies.
Main Methods:
- Generation of 3D BBB spheroids using hiPSC-derived iBCECs, primary human astrocytes, and pericytes.
- Characterization of spheroid properties, including ultrastructure, gene expression, barrier integrity, and functionality.
- Comparison of 3D spheroids against 2D mono-cultured iBCECs from distinct hiPSC lines and differentiation protocols.
Main Results:
- Spheroid properties were found to vary based on the hiPSC line and differentiation strategy used.
- The 3D spheroids exhibited in-vivo-like tight junction ultrastructure.
- Compared to 2D models, 3D spheroids showed higher transcript expression of BBB-specific genes and demonstrated characteristic barrier integrity, functionality, and protein expression.
Conclusions:
- The developed hiPSC-derived 3D BBB spheroid model more accurately represents the in-vivo microenvironment than 2D models.
- This 3D spheroid model shows significant potential as a reliable in-vitro test system for future BBB research and drug development.
