Supramolecular nanostructure mimics GDNF trophic effects in vitro on human dopaminergic neurons
Peptide-based supramolecular nanostructures offer a versatile platform with substantial promise for clinical translation in regenerative medicine. These systems allow for the incorporation of biologically active sequences and can be engineered to modulate tissue-specific parameters such as stiffness, diffusivity, and biodegradability. We developed here a bioactive supramolecular nanostructure containing a peptide designed based on glial cell-derived neurotrophic factor. These nanostructures form scaffolds that mimic important trophic effects provided by this growth factor on iPSC-derived human dopaminergic neurons. Our in vitro data show that the nanostructures promote cell viability, confer neuroprotection against 6-hydroxydopamine toxicity, enhance neuronal morphology, facilitate electrophysiological maturation, and induce genes involved in neuronal survival. We also found that the scaffold promoted axonal extension in midbrain human organoids. These findings suggest that the supramolecular system could be useful to improve outcomes in cell-based therapies for Parkinson's disease, where progressive dopaminergic degeneration is a hallmark.
Authors
- Zois Syrgiannis (ORCID: https://orcid.org/0000-0003-0345-182X)
- Stacey M. Chin (ORCID: https://orcid.org/0000-0002-2909-6080)
- Liam C. Palmer (ORCID: https://orcid.org/0000-0003-0804-1168)
- Alexandra N. Edelbrock (ORCID: https://orcid.org/0000-0003-3172-977X)
- Tamara Perez‐Rosello
- Nozomu Takata (ORCID: https://orcid.org/0000-0003-0171-6994)
- Matías Alvarez-Saavedra
- Zaida Álvarez (ORCID: https://orcid.org/0000-0001-5104-1388)
- Oscar A. Carballo-Molina (ORCID: https://orcid.org/0000-0001-5471-3389)
- Madison Strong
- Samuel Isaac Stupp (ORCID: https://orcid.org/0000-0002-5491-7442)
- Timmy Fyrner (ORCID: https://orcid.org/0000-0003-2119-9883)
- D. James Surmeier (ORCID: https://orcid.org/0000-0002-6376-5225)
Institutions
- Northwestern University (US)
- Institute for Bioengineering of Catalonia (ES)
Publication Details
- Journal
- npj Regenerative Medicine
- Published
- 2025-08-08
- DOI
- https://doi.org/10.1038/s41536-025-00424-z
- Citations
- 3
- Primary Topic
- RNA Interference and Gene Delivery
- Type
- article
- Field-Weighted Citation Impact
- 2.42
Funders
- National Science Foundation
- Foundation for the National Institutes of Health
- W. M. Keck Foundation
- Northwestern University
- Paralyzed Veterans of America
- JPB Foundation
- National Institutes of Health
- Materials Research Science and Engineering Center, Harvard University
- International Institute for Nanotechnology, Northwestern University
- National Cancer Institute
- Division of Materials Research
- Division of Electrical, Communications and Cyber Systems