Axon guidance gene-targeted siRNA delivery system improves neural stem cell transplantation therapy after spinal cord injury
Abstract Background Neural stem cells (NSCs) derived from the embryonic spinal cord are excellent candidates for the cellular regeneration of lost neural cells after spinal cord injury (SCI). Semaphorin 3 A (Sema3A) is well known as being implicated in the major axon guidance of the growth cone as a...
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2023-10-01
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| Series: | Biomaterials Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40824-023-00434-2 |
| _version_ | 1797280061630447616 |
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| author | Seong Jun Kim Wan-Kyu Ko Gong Ho Han Daye Lee Min Jai Cho Seung Hun Sheen Seil Sohn |
| author_facet | Seong Jun Kim Wan-Kyu Ko Gong Ho Han Daye Lee Min Jai Cho Seung Hun Sheen Seil Sohn |
| author_sort | Seong Jun Kim |
| collection | DOAJ |
| description | Abstract Background Neural stem cells (NSCs) derived from the embryonic spinal cord are excellent candidates for the cellular regeneration of lost neural cells after spinal cord injury (SCI). Semaphorin 3 A (Sema3A) is well known as being implicated in the major axon guidance of the growth cone as a repulsive function during the development of the central nervous system, yet its function in NSC transplantation therapy for SCI has not been investigated. Here, we report for the first time that embryonic spinal cord-derived NSCs significantly express Sema3A in the SCI environment, potentially facilitating inhibition of cell proliferation after transplantation. Methods siRNA-Sema3A was conjugated with poly-l-lysin-coated gold nanoparticles (AuNPs) through a charge interaction process. NSCs were isolated from embryonic spinal cords of rats. Then, the cells were embedded into a dual-degradable hydrogel with the siRNA- Sema3A loaded-AuNPs and transplanted after complete SCI in rats. Results The knockdown of Sema3A by delivering siRNA nanoparticles via dual-degradable hydrogels led to a significant increase in cell survival and neuronal differentiation of the transplanted NSCs after SCI. Of note, the knockdown of Sema3A increased the synaptic connectivity of transplanted NSC in the injured spinal cord. Moreover, extracellular matrix molecule and functional recovery were significantly improved in Sema3A-inhibited rats compared to those in rats with only NSCs transplanted. Conclusions These findings demonstrate the important role of Sema3A in NSC transplantation therapy, which may be considered as a future cell transplantation therapy for SCI cases. Graphical Abstract |
| first_indexed | 2024-03-07T16:34:48Z |
| format | Article |
| id | doaj.art-c2dee162e73f4d8d9e6a74ceac89b1dc |
| institution | Directory Open Access Journal |
| issn | 2055-7124 |
| language | English |
| last_indexed | 2024-03-07T16:34:48Z |
| publishDate | 2023-10-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Biomaterials Research |
| spelling | doaj.art-c2dee162e73f4d8d9e6a74ceac89b1dc2024-03-03T09:49:17ZengAmerican Association for the Advancement of Science (AAAS)Biomaterials Research2055-71242023-10-0127111510.1186/s40824-023-00434-2Axon guidance gene-targeted siRNA delivery system improves neural stem cell transplantation therapy after spinal cord injurySeong Jun Kim0Wan-Kyu Ko1Gong Ho Han2Daye Lee3Min Jai Cho4Seung Hun Sheen5Seil Sohn6Department of Neurosurgery, CHA Bundang Medical Center, CHA UniversityDepartment of Neurosurgery, CHA Bundang Medical Center, CHA UniversityDepartment of Neurosurgery, CHA Bundang Medical Center, CHA UniversityDepartment of Neurosurgery, CHA Bundang Medical Center, CHA UniversityDepartment of Neurosurgery, Chungbuk National UniversityDepartment of Neurosurgery, CHA Bundang Medical Center, CHA UniversityDepartment of Neurosurgery, CHA Bundang Medical Center, CHA UniversityAbstract Background Neural stem cells (NSCs) derived from the embryonic spinal cord are excellent candidates for the cellular regeneration of lost neural cells after spinal cord injury (SCI). Semaphorin 3 A (Sema3A) is well known as being implicated in the major axon guidance of the growth cone as a repulsive function during the development of the central nervous system, yet its function in NSC transplantation therapy for SCI has not been investigated. Here, we report for the first time that embryonic spinal cord-derived NSCs significantly express Sema3A in the SCI environment, potentially facilitating inhibition of cell proliferation after transplantation. Methods siRNA-Sema3A was conjugated with poly-l-lysin-coated gold nanoparticles (AuNPs) through a charge interaction process. NSCs were isolated from embryonic spinal cords of rats. Then, the cells were embedded into a dual-degradable hydrogel with the siRNA- Sema3A loaded-AuNPs and transplanted after complete SCI in rats. Results The knockdown of Sema3A by delivering siRNA nanoparticles via dual-degradable hydrogels led to a significant increase in cell survival and neuronal differentiation of the transplanted NSCs after SCI. Of note, the knockdown of Sema3A increased the synaptic connectivity of transplanted NSC in the injured spinal cord. Moreover, extracellular matrix molecule and functional recovery were significantly improved in Sema3A-inhibited rats compared to those in rats with only NSCs transplanted. Conclusions These findings demonstrate the important role of Sema3A in NSC transplantation therapy, which may be considered as a future cell transplantation therapy for SCI cases. Graphical Abstracthttps://doi.org/10.1186/s40824-023-00434-2Spinal cord injuriesNeural stem cellsSemaphorin-3ASmall interfering RNAAxon guidance |
| spellingShingle | Seong Jun Kim Wan-Kyu Ko Gong Ho Han Daye Lee Min Jai Cho Seung Hun Sheen Seil Sohn Axon guidance gene-targeted siRNA delivery system improves neural stem cell transplantation therapy after spinal cord injury Biomaterials Research Spinal cord injuries Neural stem cells Semaphorin-3A Small interfering RNA Axon guidance |
| title | Axon guidance gene-targeted siRNA delivery system improves neural stem cell transplantation therapy after spinal cord injury |
| title_full | Axon guidance gene-targeted siRNA delivery system improves neural stem cell transplantation therapy after spinal cord injury |
| title_fullStr | Axon guidance gene-targeted siRNA delivery system improves neural stem cell transplantation therapy after spinal cord injury |
| title_full_unstemmed | Axon guidance gene-targeted siRNA delivery system improves neural stem cell transplantation therapy after spinal cord injury |
| title_short | Axon guidance gene-targeted siRNA delivery system improves neural stem cell transplantation therapy after spinal cord injury |
| title_sort | axon guidance gene targeted sirna delivery system improves neural stem cell transplantation therapy after spinal cord injury |
| topic | Spinal cord injuries Neural stem cells Semaphorin-3A Small interfering RNA Axon guidance |
| url | https://doi.org/10.1186/s40824-023-00434-2 |
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