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

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 base...

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Main Authors: 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
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2024-05-01
Series:Bioactive Materials
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Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X24000227
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author 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
author_facet 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
author_sort Zhaoping Wu
collection DOAJ
description 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.
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spelling doaj.art-4733c1fb6a4c4c578a811ceba219ceb72024-03-29T05:50:50ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2024-05-0135242258Construction 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 repairZhaoping Wu0Yi Zhou1Xianglin Hou2Weidong Liu3Wen Yin4Lei Wang5Yudong Cao6Zhipeng Jiang7Youwei Guo8Quan Chen9Wen Xie10Ziqiang Wang11Ning Shi12Yujun Liu13Xiang Gao14Longlong Luo15Jianwu Dai16Caiping Ren17Xingjun Jiang18Department 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, ChinaDepartment 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, ChinaState Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaSchool 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, ChinaCollege of Biology, Hunan University, Changsha, 410000, ChinaSchool 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, ChinaState Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100080, ChinaState Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100080, China; Corresponding author.State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100080, China; Corresponding author.State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China; Corresponding author.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.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.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.http://www.sciencedirect.com/science/article/pii/S2452199X24000227Spinal cord injuryInduced pluripotent stem cellsLOCSNeural network tissueNeurotrophin-3
spellingShingle 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
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
Bioactive Materials
Spinal cord injury
Induced pluripotent stem cells
LOCS
Neural network tissue
Neurotrophin-3
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Spinal cord injury
Induced pluripotent stem cells
LOCS
Neural network tissue
Neurotrophin-3
url http://www.sciencedirect.com/science/article/pii/S2452199X24000227
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