Biofunctionalized gelatin hydrogels support development and maturation of iPSC-derived cortical organoids
Andrew Kjar,
Mia R. Haschert,
José C. Zepeda,
A. Joey Simmons,
Alexis Yates,
Daniel Chavarria,
Melanie Fernandez,
Gabriella Robertson,
Adam M. Abdulrahman,
Hyosung Kim,
Nicole T. Marguerite,
Rachel K. Moen,
Lauren E. Drake,
Corinne W. Curry,
Brian J. O’Grady,
Vivian Gama,
Ken S. Lau,
Brad Grueter,
Jonathan M. Brunger,
Ethan S. Lippmann
Affiliations
Andrew Kjar
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA
Mia R. Haschert
Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA
José C. Zepeda
Department of Pharmacology, Vanderbilt University, Nashville, TN, USA
A. Joey Simmons
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA
Alexis Yates
Interdisciplinary Materials Science Program, Vanderbilt University, Nashville, TN, USA
Daniel Chavarria
Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA
Melanie Fernandez
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA
Gabriella Robertson
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA
Adam M. Abdulrahman
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA
Hyosung Kim
Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA
Nicole T. Marguerite
Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA
Rachel K. Moen
Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA
Lauren E. Drake
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA
Corinne W. Curry
Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA
Brian J. O’Grady
Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA
Vivian Gama
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA; Vanderbilt Center for Stem Cell Biology, Vanderbilt University, Nashville, TN, USA
Ken S. Lau
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Center for Stem Cell Biology, Vanderbilt University, Nashville, TN, USA; Chemical and Physical Biology Program, Vanderbilt University School of Medicine, Nashville, TN, USA; Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
Brad Grueter
Department of Pharmacology, Vanderbilt University, Nashville, TN, USA; Department of Anesthesiology, Vanderbilt University, Nashville, TN, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN, USA
Jonathan M. Brunger
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA; Vanderbilt Center for Stem Cell Biology, Vanderbilt University, Nashville, TN, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
Ethan S. Lippmann
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA; Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA; Interdisciplinary Materials Science Program, Vanderbilt University, Nashville, TN, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA; Vanderbilt Center for Stem Cell Biology, Vanderbilt University, Nashville, TN, USA; Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Memory and Alzheimer’s Center, Vanderbilt University Medical Center, Nashville, TN, USA; Corresponding author
Summary: 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.
