Transplantation of engineered spinal cord organoids restores functions after spinal cord injury.

Journal: Brain : a journal of neurology
Published Date: Sep 7, 2026

Abstract

Generating functional maturation neural organoids to model degenerative disease or replace large damaged central nervous tissue remains an enormous challenge. Here, we developed a novel blood vessel-mimicking nanomaterial system by combining carboxylated cellulose nanofibres (CCN) with Matrigel to create biosafety scaffolds. These engineered scaffolds demonstrated a remarkable capacity to support the long-term growth over 300 days and functional maturation of neural organoids, enabling the development of centimetre-scale organoids without necrotic cores. CCN-engineered human spinal cord organoids (ChSOs) could self-elongate axon tracts, robustly form axon myelination and establish functional neural networks. Following transplantation, ChSOs demonstrated remarkable differentiation potential, generating multiple subtypes of spinal cord neurons, both dorsal and ventral, that could migrate and integrate sufficiently with the host spinal cord tissue. Notably, these grafted ChSOs secrete the axon guidance factor NTN1, enhancing axonogenesis and facilitating the restoration of sensory and motor functions in mice with complete spinal cord injury. These findings show that ChSOs provide a platform for studying neural development and achieving functional spinal cord repair.

Authors

  • Linlin Liu
    Hengyang Medical School, School of Nursing, University of South China, Hengyang, People's Republic of China.
  • Weiwei Xue
    School of Pharmaceutical Sciences, Chongqing University, Chongqing, China.
  • Yufei Kong
    Department of Neurology, Zhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Brain Function and Disorders, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China.
  • Huijuan Li
    School of Pharmaceutical Sciences, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250014, China.
  • Qi Fan
    Department of Rehabilitation Medicine Center, Affiliated Tai'an Central Hospital, Qingdao University, No. 29, Longtan Road, Taishan District, Tai'an City, 271000, Shandong, China.
  • Jingyi Shi
    Department of Neurology, Zhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Brain Function and Disorders, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China.
  • Huihui Liu
    Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China. [email protected].
  • Jinhong Xu
    Department of Neurology, Zhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Brain Function and Disorders, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China.
  • Yujie Xiao
    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.
  • Hongli Wang
    Breast Tumor Center.
  • Bo Li
    Electric Power Research Institute, Yunnan Power Grid Co., Ltd., Kunming, Yunnan, China.
  • Shengxi Wu
    School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, 400054, China.
  • Zhicheng Shao
    Department of Neurology, Zhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Brain Function and Disorders, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.

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