2. Academic Validation
  3. Preclinical long-term safety of intraspinal transplantation of human dorsal spinal GABA neural progenitor cells

Preclinical long-term safety of intraspinal transplantation of human dorsal spinal GABA neural progenitor cells

  • iScience. 2023 Oct 23;26(11):108306. doi: 10.1016/j.isci.2023.108306.
Xiaolong Zheng 1,  Zhixian Liu 1,  Ziyu He 1,  Jia Xu 2 3,  YaNan Wang 2,  ChenZi Gong 2,  Ruoying Zhang 1,  Su-Chun Zhang 4 5,  Hong Chen 2 3 6,  Wei Wang 1 6 7
Affiliations

Affiliations

  • 1 Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 2 Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 3 Stem Cell Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 4 Waisman Center, Department of Neuroscience and Department of Neurology, University of Wisconsin, Madison, WI, USA.
  • 5 Program in Neuroscience & Behavioral Disorders, Duke-NUS Medical School, Singapore, Singapore.
  • 6 Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 7 Key Laboratory of Neurological Diseases of Chinese Ministry of Education, the School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
PMID: 38026209 DOI: 10.1016/j.isci.2023.108306
Abstract

Human pluripotent stem cell (hPSC)-derived neurons have shown promise in treating spinal cord injury (SCI). We previously showed that hPSC-derived dorsal spinal γ-aminobutyric acid (GABA) neurons can alleviate spasticity and promote locomotion in rats with SCI, but their long-term safety remains elusive. Here, we characterized the long-term fate and safety of human dorsal spinal GABA neural progenitor cells (NPCs) in naive rats over one year. All grafted NPCs had undergone differentiation, yielding mainly neurons and astrocytes. Fully mature human neurons grew many axons and formed numerous synapses with rat neural circuits, together with mature human astrocytes that structurally integrated into the rat spinal cord. The sensorimotor function of rats was not impaired by intraspinal transplantation, even when human neurons were activated or inhibited by designer receptors exclusively activated by designer drugs (DREADDs). These findings represent a significant step toward the clinical translation of human spinal neuron transplantation for treating SCI.

Keywords

Biological sciences; Neuroscience.

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