生物功能化明胶水凝胶支持iPSC来源皮层类器官的发育与成熟

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

Cell Reports

影响因子:6.9

分区:生物学1区 Top / 细胞生物学2区

发表日期:2024 Nov 26

作者: 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

DOI: 10.1016/j.celrep.2024.114874

摘要

人类神经类器官模型已成为研究神经生物学的重要工具。然而，改善此类类器官中神经细胞群的代表性仍是主要挑战。在本研究中，我们比较了商用基质Matrigel与一种神经钙粘蛋白（N-cadherin）肽功能化的明胶甲基丙烯酰酯（GelMA）水凝胶（称为GelMA-Cad）在培养皮层神经类器官中的效果。结果显示，肽的呈现可以调控明胶基基质中的细胞命运和多样性。特别是，在GelMA-Cad水凝胶中培养的皮层类器官更接近人类胎儿细胞群，且产生的神经元表现出更多的自发兴奋性突触后电流。这些结果提供了有力证据，说明基质绑定的信号肽可以影响神经类器官的分化，为控制干细胞命运开辟了新途径。此工作还展示了GelMA-Cad作为一种简单、定义明确的水凝胶替代品在神经类器官培养中的潜在应用。

Abstract

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.