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Grafted human-induced pluripotent stem cells-derived oligodendrocyte progenitor cells combined with human umbilical vein endothelial cells contribute to functional recovery following spinal cord injury

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机构: [1]Cell Therapy Center, Beijing Institute of Geriatrics, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases, and Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, China. [2]Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, 100069, China. [3]Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing, 100069, China. [4]Translational Medicine Research Group (TMRG), Aston Medical School, Aston University, Birmingham, B4 7ET, UK. [5]Department of Clinical Neurosciences, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK. [6]Cell Therapy Center, Beijing Institute of Geriatrics, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases, and Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, China. [7]Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, 100069, China. [8]Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing, 100069, China.
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关键词: Spinal cord injury Induced pluripotent stem cells Oligodendrocyte progenitor cells HUVECs

摘要:
Spinal cord injury (SCI) is a devastating disease that causes extensive damage to oligodendrocytes and neurons leading to demyelination and axonal degeneration. In this study, we co-transplanted cell grafts containing oligodendrocyte progenitor cells (OPCs) derived from human-induced pluripotent stem cells (iPSCs) combined with human umbilical vein endothelial cells (HUVECs), which were reported to promote OPCs survival and migration, into rat contusion models to promote functional recovery after SCI.OPCs were derived from iPSCs and identified by immunofluorescence at different time points. Functional assays in vitro were performed to evaluate the effect of HUVECs on the proliferation, migration, and survival of OPCs by co-culture and migration assay, as well as on the neuronal axonal growth. A combination of OPCs and HUVECs was transplanted into the rat contusive model. Upon 8 weeks, immunofluorescence staining was performed to test the safety of transplanted cells and to observe the neuronal repairment, myelination, and neural circuit reconstruction at the injured area; also, the functional recovery was assessed by Basso, Beattie, and Bresnahan open-field scale, Ladder climb, SEP, and MEP. Furthermore, the effect of HUVECs on grafts was also determined in vivo.Data showed that HUVECs promote the proliferation, migration, and survival of OPCs both in vitro and in vivo. Furthermore, 8 weeks upon engraftment, the rats with OPCs and HUVECs co-transplantation noticeably facilitated remyelination, enhanced functional connection between the grafts and the host and promoted functional recovery. In addition, compared with the OPCs-alone transplantation, the co-transplantation generated more sensory neurons at the lesion border and significantly improved the sensory functional recovery.Our study demonstrates that transplantation of OPCs combined with HUVECs significantly enhances both motor and sensory functional recovery after SCI. No significance was observed between OPCs combined with HUVECs group and OPCs-alone group in motor function recovery, while the sensory function recovery was significantly promoted in OPCs combined with HUVECs groups compared with the other two groups. These findings provide novel insights into the field of SCI research.© 2024. The Author(s).

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出版当年[2023]版:
大类 | 2 区 医学
小类 | 2 区 细胞与组织工程 2 区 细胞生物学 2 区 医学:研究与实验
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 细胞与组织工程 2 区 细胞生物学 2 区 医学:研究与实验
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出版当年[2022]版:
Q1 CELL & TISSUE ENGINEERING Q1 CELL BIOLOGY Q1 MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版:
Q1 CELL & TISSUE ENGINEERING Q1 CELL BIOLOGY Q1 MEDICINE, RESEARCH & EXPERIMENTAL

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第一作者机构: [1]Cell Therapy Center, Beijing Institute of Geriatrics, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases, and Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, China. [2]Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, 100069, China. [3]Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing, 100069, China.
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通讯机构: [6]Cell Therapy Center, Beijing Institute of Geriatrics, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases, and Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, China. [7]Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, 100069, China. [8]Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing, 100069, China.
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