Biofunctionalized gelatin hydrogels support development and maturation of iPSC-derived cortical organoids

• Published in: Cell reports (Cambridge) Vol. 43; no. 11; p. 114874
• Main Authors: Kjar, Andrew, Haschert, Mia R., Zepeda, José C., Simmons, A. Joey, Yates, Alexis, Chavarria, Daniel, Fernandez, Melanie, Robertson, Gabriella, Abdulrahman, Adam M., Kim, Hyosung, Marguerite, Nicole T., Moen, Rachel K., Drake, Lauren E., Curry, Corinne W., O’Grady, Brian J., Gama, Vivian, Lau, Ken S., Grueter, Brad, Brunger, Jonathan M., Lippmann, Ethan S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26-11-2024; Elsevier
• Subjects: CP: Stem cell research; GelMA; Matrigel; N-cadherin; neural organoids; peptide-functionalized matrices; neural organoids; GelMA; CP: Stem cell research; N-cadherin; Matrigel; peptide-functionalized matrices
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.114874

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.
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•Peptide-functionalized gelatin (GelMA-Cad) hydrogels support neural organoids•Peptide presence influences long-term cell trajectories and neural fate•GelMA-Cad aids maturation of neurons within organoids•Organoids in GelMA-Cad map closely to human fetal populations
Neural organoids are widely used models of the developing brain. In this work, Kjar et al. compare the development of organoids in a commercial biomaterial (Matrigel) versus a peptide-functionalized gelatin matrix (GelMA-Cad). The biomimetic N-cadherin peptide on GelMA-Cad is shown to reinforce neural fate and aid maturation relative to Matrigel.