Construction of functional neural network tissue combining CBD-NT3-modified linear-ordered collagen scaffold and TrkC-modified iPSC-derived neural stem cells for spinal cord injury repair

Zhaoping Wu; Yi Zhou; Xianglin Hou; Weidong Liu; Wen Yin; Lei Wang; Yudong Cao; Zhipeng Jiang; Youwei Guo; Quan Chen; Wen Xie; Ziqiang Wang; Ning Shi; Yujun Liu; Xiang Gao; Longlong Luo; Jianwu Dai; Caiping Ren; Xingjun Jiang

doi:10.1016/j.bioactmat.2024.01.012

Construction of functional neural network tissue combining CBD-NT3-modified linear-ordered collagen scaffold and TrkC-modified iPSC-derived neural stem cells for spinal cord injury repair

Bioact Mater. 2024 Feb 3:35:242-258. doi: 10.1016/j.bioactmat.2024.01.012. eCollection 2024 May.

Authors

Zhaoping Wu^{1

2}, Yi Zhou^{1

2}, Xianglin Hou³, Weidong Liu^{1

4

5}, Wen Yin^{1

2}, Lei Wang^{1

4

5}, Yudong Cao^{1

2}, Zhipeng Jiang^{1

2}, Youwei Guo^{1

2}, Quan Chen^{1

2}, Wen Xie^{4

5}, Ziqiang Wang⁶, Ning Shi^{4

5

7}, Yujun Liu⁷, Xiang Gao⁷, Longlong Luo⁷, Jianwu Dai³, Caiping Ren^{1

2

4

5}, Xingjun Jiang^{1

2}

Affiliations

¹ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China.
² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China.
³ State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China.
⁴ School of Basic Medical Science, Central South University, Changsha, Hunan Province, 410078, China.
⁵ The NHC Key Laboratory of Carcinogenesis and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, Hunan Province, 410078, China.
⁶ College of Biology, Hunan University, Changsha, 410000, China.
⁷ State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100080, China.

Abstract

Induced pluripotent stem cells (iPSCs) can be personalized and differentiated into neural stem cells (NSCs), thereby effectively providing a source of transplanted cells for spinal cord injury (SCI). To further improve the repair efficiency of SCI, we designed a functional neural network tissue based on TrkC-modified iPSC-derived NSCs and a CBD-NT3-modified linear-ordered collagen scaffold (LOCS). We confirmed that transplantation of this tissue regenerated neurons and synapses, improved the microenvironment of the injured area, enhanced remodeling of the extracellular matrix, and promoted functional recovery of the hind limbs in a rat SCI model with complete transection. RNA sequencing and metabolomic analyses also confirmed the repair effect of this tissue from multiple perspectives and revealed its potential mechanism for treating SCI. Together, we constructed a functional neural network tissue using human iPSCs-derived NSCs as seed cells based on the interaction of receptors and ligands for the first time. This tissue can effectively improve the therapeutic effect of SCI, thus confirming the feasibility of human iPSCs-derived NSCs and LOCS for SCI repair and providing a valuable direction for SCI research.

Keywords: Induced pluripotent stem cells; LOCS; Neural network tissue; Neurotrophin-3; Spinal cord injury.