Bioactive Materials (May 2024)
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
Affiliations
- Zhaoping Wu
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China
- Yi Zhou
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China
- Xianglin Hou
- State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China
- Weidong Liu
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; School of Basic Medical Science, Central South University, Changsha, Hunan Province, 410078, China; 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
- Wen Yin
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China
- Lei Wang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; School of Basic Medical Science, Central South University, Changsha, Hunan Province, 410078, China; 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
- Yudong Cao
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China
- Zhipeng Jiang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China
- Youwei Guo
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China
- Quan Chen
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China
- Wen Xie
- School of Basic Medical Science, Central South University, Changsha, Hunan Province, 410078, China; 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
- Ziqiang Wang
- College of Biology, Hunan University, Changsha, 410000, China
- Ning Shi
- School of Basic Medical Science, Central South University, Changsha, Hunan Province, 410078, China; 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; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100080, China
- Yujun Liu
- State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100080, China
- Xiang Gao
- State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100080, China; Corresponding author.
- Longlong Luo
- State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100080, China; Corresponding author.
- Jianwu Dai
- State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China; Corresponding author.
- Caiping Ren
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; School of Basic Medical Science, Central South University, Changsha, Hunan Province, 410078, China; 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; Corresponding authors. School of Basic Medical Science, Central South University, Changsha, Hunan Province, 410078, China.
- Xingjun Jiang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; Corresponding author. Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China.
- Journal volume & issue
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Vol. 35
pp. 242 – 258
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.