Human iPSC-derived spinal neural progenitors enhance sensorimotor recovery in spinal cord-injured NOD-SCID mice via differentiation and microenvironment regulation
Abstract Spinal cord injury (SCI) remains a significant clinical challenge and poses a dramatic threat to the life quality of patients due to limited neural regeneration and detrimental post-injury alternations in tissue microenvironment. We developed a therapeutic approach by transplanting spinal n...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-08-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07961-x |
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| author | Xuanbao Yao Kehua Zhang Tao Na Yuchun Wang Yuhan Guo Jiajie Xi Xiang Li Shufang Meng Miao Xu |
| author_facet | Xuanbao Yao Kehua Zhang Tao Na Yuchun Wang Yuhan Guo Jiajie Xi Xiang Li Shufang Meng Miao Xu |
| author_sort | Xuanbao Yao |
| collection | DOAJ |
| description | Abstract Spinal cord injury (SCI) remains a significant clinical challenge and poses a dramatic threat to the life quality of patients due to limited neural regeneration and detrimental post-injury alternations in tissue microenvironment. We developed a therapeutic approach by transplanting spinal neural progenitor cells (spNPGs), derived from human induced pluripotent stem cell (iPSC)-generated neuromesodermal progenitors, into a contusive SCI model in NOD-SCID mice. Single-cell RNA sequencing mapped the in vitro differentiation of iPSC-spNPGs, confirming their specification into spinal neuronal lineages. Single-nucleus transcriptomics at 1 week post-transplantation showed that the grafted cells differentiated in vivo into motor neurons and two interneuron subtypes (V2 and dI4). Additionally, spNPGs integrated into host neural circuits, enhancing synaptic connectivity, while simultaneously modulating the injury microenvironment by shifting microglia and astrocyte polarization toward anti-inflammatory and neuroprotective phenotypes. This dual mechanism promoted axonal regrowth, remyelination, and significant sensorimotor recovery, as evidenced by improved locomotor scores. Our findings highlight the therapeutic potential of human iPSC-spNPGs in reconstructing neural networks and mitigating secondary damage, providing compelling preclinical evidence for advancing stem cell-based SCI therapies. |
| format | Article |
| id | doaj-art-c4d4e9fa6b1e417f98fe178689a41e9c |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-c4d4e9fa6b1e417f98fe178689a41e9c2025-08-24T11:54:31ZengNature Publishing GroupCell Death and Disease2041-48892025-08-0116111410.1038/s41419-025-07961-xHuman iPSC-derived spinal neural progenitors enhance sensorimotor recovery in spinal cord-injured NOD-SCID mice via differentiation and microenvironment regulationXuanbao Yao0Kehua Zhang1Tao Na2Yuchun Wang3Yuhan Guo4Jiajie Xi5Xiang Li6Shufang Meng7Miao Xu8Graduate School of Guangzhou Medical University, Guangzhou Medical UniversityNational Institutes for Food and Drug ControlNational Institutes for Food and Drug ControlNational Institutes for Food and Drug ControlNational Institutes for Food and Drug ControlXellSmart Biomedical (Suzhou) Co., LtdXellSmart Biomedical (Suzhou) Co., LtdNational Institutes for Food and Drug ControlGuangzhou National LaboratoryAbstract Spinal cord injury (SCI) remains a significant clinical challenge and poses a dramatic threat to the life quality of patients due to limited neural regeneration and detrimental post-injury alternations in tissue microenvironment. We developed a therapeutic approach by transplanting spinal neural progenitor cells (spNPGs), derived from human induced pluripotent stem cell (iPSC)-generated neuromesodermal progenitors, into a contusive SCI model in NOD-SCID mice. Single-cell RNA sequencing mapped the in vitro differentiation of iPSC-spNPGs, confirming their specification into spinal neuronal lineages. Single-nucleus transcriptomics at 1 week post-transplantation showed that the grafted cells differentiated in vivo into motor neurons and two interneuron subtypes (V2 and dI4). Additionally, spNPGs integrated into host neural circuits, enhancing synaptic connectivity, while simultaneously modulating the injury microenvironment by shifting microglia and astrocyte polarization toward anti-inflammatory and neuroprotective phenotypes. This dual mechanism promoted axonal regrowth, remyelination, and significant sensorimotor recovery, as evidenced by improved locomotor scores. Our findings highlight the therapeutic potential of human iPSC-spNPGs in reconstructing neural networks and mitigating secondary damage, providing compelling preclinical evidence for advancing stem cell-based SCI therapies.https://doi.org/10.1038/s41419-025-07961-x |
| spellingShingle | Xuanbao Yao Kehua Zhang Tao Na Yuchun Wang Yuhan Guo Jiajie Xi Xiang Li Shufang Meng Miao Xu Human iPSC-derived spinal neural progenitors enhance sensorimotor recovery in spinal cord-injured NOD-SCID mice via differentiation and microenvironment regulation Cell Death and Disease |
| title | Human iPSC-derived spinal neural progenitors enhance sensorimotor recovery in spinal cord-injured NOD-SCID mice via differentiation and microenvironment regulation |
| title_full | Human iPSC-derived spinal neural progenitors enhance sensorimotor recovery in spinal cord-injured NOD-SCID mice via differentiation and microenvironment regulation |
| title_fullStr | Human iPSC-derived spinal neural progenitors enhance sensorimotor recovery in spinal cord-injured NOD-SCID mice via differentiation and microenvironment regulation |
| title_full_unstemmed | Human iPSC-derived spinal neural progenitors enhance sensorimotor recovery in spinal cord-injured NOD-SCID mice via differentiation and microenvironment regulation |
| title_short | Human iPSC-derived spinal neural progenitors enhance sensorimotor recovery in spinal cord-injured NOD-SCID mice via differentiation and microenvironment regulation |
| title_sort | human ipsc derived spinal neural progenitors enhance sensorimotor recovery in spinal cord injured nod scid mice via differentiation and microenvironment regulation |
| url | https://doi.org/10.1038/s41419-025-07961-x |
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