Improved brain organoid formation by synthetic extracellular matrices
2023
University of Michigan, Ann Arbor, USA
Although brain organoids mimic the human brain's cell-to-cell network interactions, they generally fail to faithfully recapitulate cell-to-matrix interactions. Here, an engineered framework, called an engineered extracellular matrix (EECM), was developed to provide support and cell-to-matrix interactions to developing brain organoids.
Brain organoids were generated using EECMs comprised of human fibrillar fibronectin supported by a highly porous polymer scaffold. These brain organoids were characterized by immunofluorescence microscopy, transcriptomics, and proteomics of the cerebrospinal fluid (CSF) compartment.
The interstitial matrix-mimicking EECM enhanced neurogenesis, glial maturation, and neuronal diversity from human embryonic stem cells versus conventional protein matrix (Matrigel). Additionally, EECMs supported long-term culture, which promoted large-volume organoids containing over 250 μL of CSF. Proteomics analysis of the CSF found it superseded previous brain organoids in protein diversity, as indicated by 280 proteins spanning 500 gene ontology pathways shared with adult CSF.
Engineered EECM matrices represent a major advancement in neural engineering as they have the potential to significantly enhance the structural, cellular, and functional diversity that can be achieved in advanced brain models.
Engineered extracellular matrices facilitate brain organoids from human pluripotent stem cells
Eva L. Feldman, Joerg Lahann
Added on: 07-20-2023
[1] https://onlinelibrary.wiley.com/doi/10.1002/acn3.51820?emci=2942ffe9-c724-ee11-a9bb-00224832eb73&emdi=ab0a670d-ae25-ee11-a9bb-00224832eb73&ceid=2015591
