Biofunctionalized gelatin hydrogels support development and maturation of iPSC-derived cortical organoids
Human neural organoid models have become an important tool for studying neurobiology. However, improving the representativeness of neural cell populations in such organoids remains a major effort. In this work, we compared Matrigel, a commercially available matrix, to a neural cadherin (N-cadherin) peptide-functionalized gelatin methacryloyl hydrogel (termed GelMA-Cad) for culturing cortical neural organoids. We determined that peptide presentation can tune cell fate and diversity in gelatin-based matrices during differentiation. Of particular note, cortical organoids cultured in GelMA-Cad hydrogels mapped more closely to human fetal populations and produced neurons with more spontaneous excitatory postsynaptic currents relative to Matrigel. These results provide compelling evidence that matrix-tethered signaling peptides can influence neural organoid differentiation, opening an avenue to control stem cell fate. Moreover, outcomes from this work showcase the technical utility of GelMA-Cad as a simple and defined hydrogel alternative to Matrigel for neural organoid culture.
Authors
- José C. Zepeda (ORCID: https://orcid.org/0000-0002-8045-4883)
- Brad A. Grueter (ORCID: https://orcid.org/0000-0002-4224-3866)
- Hyosung Kim (ORCID: https://orcid.org/0000-0003-3568-6500)
- Miriam Fernández (ORCID: https://orcid.org/0000-0003-4273-5227)
- Gabriella L. Robertson (ORCID: https://orcid.org/0000-0002-8729-8334)
- Aaron B. Simmons
- A K Yates (ORCID: https://orcid.org/0000-0003-3539-3994)
- Brian J. O’Grady (ORCID: https://orcid.org/0000-0002-4648-5096)
- Daniel Chavarría (ORCID: https://orcid.org/0000-0002-6042-2825)
- Lauren E. Drake (ORCID: https://orcid.org/0000-0003-1067-479X)
- Ethan S. Lippmann (ORCID: https://orcid.org/0000-0001-5703-5747)
- Ken S. Lau (ORCID: https://orcid.org/0000-0001-8438-0319)
- Nicole T. Marguerite
- Jonathan M. Brunger (ORCID: https://orcid.org/0000-0001-7468-7982)
- Vivian Gama (ORCID: https://orcid.org/0000-0002-1201-1394)
- Andrew Kjar (ORCID: https://orcid.org/0000-0001-5402-8752)
- Corinne W. Curry
- Adam M Abdulrahman (ORCID: https://orcid.org/0000-0002-6424-3162)
- Rachel K Moen
- Mia R Haschert
Institutions
- Vanderbilt University (US)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-10-17
- DOI
- https://doi.org/10.1016/j.celrep.2024.114874
- Citations
- 26
- Primary Topic
- 3D Printing in Biomedical Research
- Type
- article
- Field-Weighted Citation Impact
- 4.80
Funders
- National Science Foundation
- Howard Hughes Medical Institute
- Vanderbilt University
- Chan Zuckerberg Initiative
- National Institutes of Health
- National Institute on Aging
- National Institute of Diabetes and Digestive and Kidney Diseases