2. Academic Validation
  3. Generation of neural organoids for spinal-cord regeneration via the direct reprogramming of human astrocytes

Generation of neural organoids for spinal-cord regeneration via the direct reprogramming of human astrocytes

  • Nat Biomed Eng. 2022 Nov 24. doi: 10.1038/s41551-022-00963-6.
Jinhong Xu # 1 2,  Shi Fang # 1 2,  Suixin Deng 1,  Huijuan Li 1,  Xiaoning Lin 3,  Yongheng Huang 1 2,  Sangmi Chung 4,  Yousheng Shu 1,  Zhicheng Shao 5 6
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, China.
  • 2 Fujian Provincial Key Laboratory of Neurodegenerative, Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, Fujian, China.
  • 3 Department of Neurosurgery, Zhongshan Hospital Xiamen University, Xiamen, Fujian, China.
  • 4 Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY, USA.
  • 5 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, China. zcshao@fudan.edu.cn.
  • 6 Fujian Provincial Key Laboratory of Neurodegenerative, Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, Fujian, China. zcshao@fudan.edu.cn.
  • # Contributed equally.
PMID: 36424465 DOI: 10.1038/s41551-022-00963-6
Abstract

Organoids with region-specific architecture could facilitate the repair of injuries of the central nervous system. Here we show that human astrocytes can be directly reprogrammed into early neuroectodermal cells via the overexpression of OCT4, the suppression of p53 and the provision of the small molecules CHIR99021, SB431542, RepSox and Y27632. We also report that the activation of signalling mediated by Fibroblast Growth Factor, sonic Hedgehog and bone morphogenetic protein 4 in the reprogrammed cells induces them to form spinal-cord organoids with functional neurons specific to the dorsal and ventral domains. In mice with complete spinal-cord injury, organoids transplanted into the lesion differentiated into spinal-cord neurons, which migrated and formed synapses with host neurons. The direct reprogramming of human astrocytes into neurons may pave the way for in vivo neural organogenesis from endogenous astrocytes for the repair of injuries to the central nervous system.

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