Bioactive Materials (Sep 2023)
Engineered human spinal cord-like tissues with dorsal and ventral neuronal progenitors for spinal cord injury repair in rats and monkeys
- Bai Xu,
- Dingyang Liu,
- Weiyuan Liu,
- Ge Long,
- Wenbin Liu,
- Yayu Wu,
- Xinghui He,
- Yeyu Shen,
- Peipei Jiang,
- Man Yin,
- Yongheng Fan,
- He Shen,
- Liyang Shi,
- Qi Zhang,
- Weiwei Xue,
- Chen Jin,
- Zhenni Chen,
- Bing Chen,
- Jiayin Li,
- Yali Hu,
- Xing Li,
- Zhifeng Xiao,
- Yannan Zhao,
- Jianwu Dai
Affiliations
- Bai Xu
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China; Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
- Dingyang Liu
- Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, 410008, China; College of Life Science, Central South University, Changsha, 410078, China
- Weiyuan Liu
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
- Ge Long
- Department of Anesthesia, The Third Xiangya Hospital of Central South University, Changsha, 410013, China
- Wenbin Liu
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
- Yayu Wu
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
- Xinghui He
- Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, 410008, China; College of Life Science, Central South University, Changsha, 410078, China
- Yeyu Shen
- College of Life Science, Central South University, Changsha, 410078, China; Department of Spine Surgery, Xiangya Hospital of Central South University, Changsha, 410008, China
- Peipei Jiang
- Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China
- Man Yin
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
- Yongheng Fan
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
- He Shen
- Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China
- Liyang Shi
- College of Biology, Hunan University, Changsha, 410012, China
- Qi Zhang
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
- Weiwei Xue
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
- Chen Jin
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
- Zhenni Chen
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
- Bing Chen
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
- Jiayin Li
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
- Yali Hu
- Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China
- Xing Li
- College of Life Science, Central South University, Changsha, 410078, China; Corresponding author.
- Zhifeng Xiao
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China; Corresponding author.
- Yannan Zhao
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China; Corresponding author.
- Jianwu Dai
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China; Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China; Corresponding author. State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
- Journal volume & issue
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Vol. 27
pp. 125 – 137
Abstract
Transplanting human neural progenitor cells is a promising method of replenishing the lost neurons after spinal cord injury (SCI), but differentiating neural progenitor cells into the diverse types of mature functional spinal cord neurons in vivo is challenging. In this study, engineered human embryonic spinal cord-like tissues with dorsal and ventral neuronal characters (DV-SC) were generated by inducing human neural progenitor cells (hscNPCs) to differentiate into various types of dorsal and ventral neuronal cells on collagen scaffold in vitro. Transplantation of DV-SC into complete SCI models in rats and monkeys showed better therapeutic effects than undifferentiated hscNPCs, including pronounced cell survival and maturation. DV-SC formed a targeted connection with the host's ascending and descending axons, partially restored interrupted neural circuits, and improved motor evoked potentials and the hindlimb function of animals with SCI. This suggests that the transplantation of pre-differentiated hscNPCs with spinal cord dorsal and ventral neuronal characteristics could be a promising strategy for SCI repair.
