2. Academic Validation
  3. Generation of dorsoventral human spinal cord organoids via functionalizing composite scaffold for drug testing

Generation of dorsoventral human spinal cord organoids via functionalizing composite scaffold for drug testing

  • iScience. 2022 Dec 26;26(1):105898. doi: 10.1016/j.isci.2022.105898.
Weiwei Xue 1,  Bo Li 1 2,  Huihui Liu 1,  Yujie Xiao 3,  Bo Li 3,  Lei Ren 2,  Huijuan Li 1,  Zhicheng Shao 1
Affiliations

Affiliations

  • 1 Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Pediatrics, National Children's Medical Center, Children's Hospital, Fudan University, Shanghai 200032, China.
  • 2 Key Laboratory of Biomedical Engineering of Fujian Province University/Research Center of Biomedical Engineering of Xiamen, Department of Biomaterials, College of Materials, Xiamen University, Xiamen 361005, China.
  • 3 Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China.
PMID: 36647382 DOI: 10.1016/j.isci.2022.105898
Abstract

The spinal cord possesses highly complex, finely organized cytoarchitecture guided by two dorsoventral morphogenic organizing centers. Thus, generation of human spinal cord tissue in vitro is challenging. Here, we demonstrated a novel method for generation of human dorsoventral spinal cord organoids using composite scaffolds. Specifically, the spinal cord ventralizing signaling Shh agonist (SAG) was loaded into a porous chitosan microsphere (PCSM), then thermosensitive Matrigel was coated on the surface to form composite microspheres with functional sustained-release SAG, termed as PCSM-Matrigel@SAG. Using PCSM-Matrigel@SAG as the core to induce 3D engineering of human spinal cord organoids from human pluripotent stem cells (ehSC-organoids), we found ehSC-organoids could form dorsoventral spinal cord-like cytoarchitecture with major domain-specific progenitors and neurons. Besides, these ehSC-organoids also showed functional calcium activity. In summary, these ehSC-organoids are of great significance for modeling spinal cord development, drug screening as 3D models for motor neuron diseases, and spinal cord injury repair.

Keywords

Biomaterials; Materials science; Neuroscience.

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