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
Abstract Background 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-ind...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-02-01
|
| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-024-03651-1 |
| _version_ | 1797275601905647616 |
|---|---|
| author | Qian Li Sumei Liu Tianqi Zheng Mo Li Boling Qi Liping Zhou Bochao Liu Dan Ma Chao Zhao Zhiguo Chen |
| author_facet | Qian Li Sumei Liu Tianqi Zheng Mo Li Boling Qi Liping Zhou Bochao Liu Dan Ma Chao Zhao Zhiguo Chen |
| author_sort | Qian Li |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusions 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. |
| first_indexed | 2024-03-07T15:16:49Z |
| format | Article |
| id | doaj.art-24610c184768436194b538c588348a72 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-03-07T15:16:49Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-24610c184768436194b538c588348a722024-03-05T17:52:13ZengBMCStem Cell Research & Therapy1757-65122024-02-0115112010.1186/s13287-024-03651-1Grafted human-induced pluripotent stem cells-derived oligodendrocyte progenitor cells combined with human umbilical vein endothelial cells contribute to functional recovery following spinal cord injuryQian Li0Sumei Liu1Tianqi Zheng2Mo Li3Boling Qi4Liping Zhou5Bochao Liu6Dan Ma7Chao Zhao8Zhiguo Chen9Cell 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 EducationCell 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 EducationCell 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 EducationCell 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 EducationCell 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 EducationCell 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 EducationCell 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 EducationTranslational Medicine Research Group (TMRG), Aston Medical School, Aston UniversityDepartment of Clinical Neurosciences, Wellcome Trust-Medical Research Council Stem Cell Institute, University of CambridgeCell 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 EducationAbstract Background 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. Methods 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. Results 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. Conclusions 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.https://doi.org/10.1186/s13287-024-03651-1Spinal cord injuryInduced pluripotent stem cellsOligodendrocyte progenitor cellsHUVECs |
| spellingShingle | Qian Li Sumei Liu Tianqi Zheng Mo Li Boling Qi Liping Zhou Bochao Liu Dan Ma Chao Zhao Zhiguo Chen 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 Stem Cell Research & Therapy Spinal cord injury Induced pluripotent stem cells Oligodendrocyte progenitor cells HUVECs |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Spinal cord injury Induced pluripotent stem cells Oligodendrocyte progenitor cells HUVECs |
| url | https://doi.org/10.1186/s13287-024-03651-1 |
| work_keys_str_mv | AT qianli graftedhumaninducedpluripotentstemcellsderivedoligodendrocyteprogenitorcellscombinedwithhumanumbilicalveinendothelialcellscontributetofunctionalrecoveryfollowingspinalcordinjury AT sumeiliu graftedhumaninducedpluripotentstemcellsderivedoligodendrocyteprogenitorcellscombinedwithhumanumbilicalveinendothelialcellscontributetofunctionalrecoveryfollowingspinalcordinjury AT tianqizheng graftedhumaninducedpluripotentstemcellsderivedoligodendrocyteprogenitorcellscombinedwithhumanumbilicalveinendothelialcellscontributetofunctionalrecoveryfollowingspinalcordinjury AT moli graftedhumaninducedpluripotentstemcellsderivedoligodendrocyteprogenitorcellscombinedwithhumanumbilicalveinendothelialcellscontributetofunctionalrecoveryfollowingspinalcordinjury AT bolingqi graftedhumaninducedpluripotentstemcellsderivedoligodendrocyteprogenitorcellscombinedwithhumanumbilicalveinendothelialcellscontributetofunctionalrecoveryfollowingspinalcordinjury AT lipingzhou graftedhumaninducedpluripotentstemcellsderivedoligodendrocyteprogenitorcellscombinedwithhumanumbilicalveinendothelialcellscontributetofunctionalrecoveryfollowingspinalcordinjury AT bochaoliu graftedhumaninducedpluripotentstemcellsderivedoligodendrocyteprogenitorcellscombinedwithhumanumbilicalveinendothelialcellscontributetofunctionalrecoveryfollowingspinalcordinjury AT danma graftedhumaninducedpluripotentstemcellsderivedoligodendrocyteprogenitorcellscombinedwithhumanumbilicalveinendothelialcellscontributetofunctionalrecoveryfollowingspinalcordinjury AT chaozhao graftedhumaninducedpluripotentstemcellsderivedoligodendrocyteprogenitorcellscombinedwithhumanumbilicalveinendothelialcellscontributetofunctionalrecoveryfollowingspinalcordinjury AT zhiguochen graftedhumaninducedpluripotentstemcellsderivedoligodendrocyteprogenitorcellscombinedwithhumanumbilicalveinendothelialcellscontributetofunctionalrecoveryfollowingspinalcordinjury |