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

doi:10.1016/j.bioactmat.2023.03.015

Engineered human spinal cord-like tissues with dorsal and ventral neuronal progenitors for spinal cord injury repair in rats and monkeys

Bioact Mater. 2023 Mar 29:27:125-137. doi: 10.1016/j.bioactmat.2023.03.015. eCollection 2023 Sep.

Authors

Bai Xu^{1

2}, Dingyang Liu^{3

4}, Weiyuan Liu¹, Ge Long⁵, Wenbin Liu¹, Yayu Wu¹, Xinghui He^{3

4}, Yeyu Shen^{4

6}, Peipei Jiang⁷, Man Yin¹, Yongheng Fan¹, He Shen⁸, Liyang Shi⁹, Qi Zhang¹, Weiwei Xue¹, Chen Jin¹, Zhenni Chen¹, Bing Chen¹, Jiayin Li¹, Yali Hu⁷, Xing Li⁴, Zhifeng Xiao¹, Yannan Zhao¹, Jianwu Dai^{1

8}

Affiliations

¹ State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.
² Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China.
³ Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, 410008, China.
⁴ College of Life Science, Central South University, Changsha, 410078, China.
⁵ Department of Anesthesia, The Third Xiangya Hospital of Central South University, Changsha, 410013, China.
⁶ Department of Spine Surgery, Xiangya Hospital of Central South University, Changsha, 410008, China.
⁷ Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
⁸ Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.
⁹ College of Biology, Hunan University, Changsha, 410012, China.

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.

Keywords: Neuronal progenitors; Spinal cord injury; Tissue engineering.