Fibrin hydrogels regulate human astrocyte state and neuronal reprogramming
Distler T, Vásquez Sepúlveda SI, Franze K, Goetz M, Masserdotti G
Publication Type: Journal article
Journal
Original Authors: Thomas Distler, Katherina Konrad Daga, Martina Bürkle, Sebastián Vásquez-Sepúlveda, Kristian Franze, Magdalena Götz, Giacomo Masserdotti
Pages Range: 100493
Article Number: 100493
DOI: 10.1016/j.celbio.2026.100493
Abstract
Astrocytes are key components in reactive gliosis after brain injury, yet defined in vitro models dissecting the influence of extracellular matrix components enriched after injury, such as fibrin, on human astrocyte behavior and function are still missing. Here, we use fibrinogen-derived fibrin and fibrin-alginate-RGD (FAR) 3D hydrogel substrates to examine their influence on human induced pluripotent stem cell (hiPSC)-derived astrocyte behavior and on their direct conversion into neurons. Astrocytes develop complex morphologies in 3D-FAR hydrogels, while they are more proliferative and migratory in 3D-fibrin hydrogels (3D-fibrin). Interestingly, gene expression analysis revealed different reactive states of astrocytes in 3D-fibrin and 3D-FAR, which persist over time. The highly inflammatory state and stiffness of 3D-FAR are largely incompatible with direct neuronal reprogramming, hampering the direct conversion even at early stages. Conversely, astrocytes in 3D-fibrin hydrogels can convert into neuronal cells, demonstrating a potent influence of how fibrin is presented on distinct astrocyte states, with great relevance for fate conversion.
Authors with CRIS profile
Thomas Distler
Lehrstuhl für Werkstoffwissenschaften (Korrosion und Oberflächentechnik) (LKO)
Sebastián Ignacio Vásquez Sepúlveda
Sonderforschungsbereich 1540/1 - Erforschung der Mechanik des Gehirns (EBM): Verständnis, Engineering und Nutzung mechanischer Eigenschaften und Signale in der Entwicklung, Physiologie und Pathologie des zentralen Nervensystems
Kristian Franze
Lehrstuhl für Neuronale Mechanik
Additional Organisation(s)
Involved external institutions
Germany (DE)How to cite
APA:
Distler, T., Vásquez Sepúlveda, S.I., Franze, K., Goetz, M., & Masserdotti, G. (2026). Fibrin hydrogels regulate human astrocyte state and neuronal reprogramming. Cell Biomaterials, 100493. https://doi.org/10.1016/j.celbio.2026.100493
MLA:
Distler, Thomas, et al. "Fibrin hydrogels regulate human astrocyte state and neuronal reprogramming." Cell Biomaterials (2026): 100493.
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