Self‐Healing COCu‐Tac Hydrogel Enhances iNSCs Transplantation for Spinal Cord Injury by Promoting Mitophagy via the FKBP52/AKT Pathway
Abstract In the realm of neural regeneration post‐spinal cord injury, hydrogel scaffolds carrying induced neural stem cells (iNSCs) have demonstrated significant potential. However, challenges such as graft rejection and dysfunction caused by mitochondrial damage persist after transplantation, prese...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202407757 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832593518850211840 |
|---|---|
| author | Zhenming Tian Han‐Jian Hu Chun Cheung Chan Tian Hu Chaoyang Cai Hong Li Limin Rong Gang‐Biao Jiang Bin Liu |
| author_facet | Zhenming Tian Han‐Jian Hu Chun Cheung Chan Tian Hu Chaoyang Cai Hong Li Limin Rong Gang‐Biao Jiang Bin Liu |
| author_sort | Zhenming Tian |
| collection | DOAJ |
| description | Abstract In the realm of neural regeneration post‐spinal cord injury, hydrogel scaffolds carrying induced neural stem cells (iNSCs) have demonstrated significant potential. However, challenges such as graft rejection and dysfunction caused by mitochondrial damage persist after transplantation, presenting formidable barriers. Tacrolimus, known for its dual role as an immunosuppressant and promoter of neural regeneration, holds the potential for enhancing iNSC transplantation. However, systemic administration of tacrolimus often comes with severe side effects. This study pioneers the development of a self‐healing hydrogel with sustained‐release tacrolimus (COCu‐Tac), tailored specifically for iNSC transplantation after spinal cord injury. This research reveals that the sustained release of tacrolimus enhances axonal growth and improves mitochondrial quality control in iNSCs and neurons. Further analysis shows that tacrolimus targets FKBP52 rather than FKBP51, enhancing mitophagy via the FKBP52/AKT pathway. This advanced system demonstrates significant efficacy in promoting neural regeneration and restoring motor function following spinal cord injury. |
| format | Article |
| id | doaj-art-08f1cf64ce62474893a890572b891ebe |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-08f1cf64ce62474893a890572b891ebe2025-01-20T13:04:18ZengWileyAdvanced Science2198-38442025-01-01123n/an/a10.1002/advs.202407757Self‐Healing COCu‐Tac Hydrogel Enhances iNSCs Transplantation for Spinal Cord Injury by Promoting Mitophagy via the FKBP52/AKT PathwayZhenming Tian0Han‐Jian Hu1Chun Cheung Chan2Tian Hu3Chaoyang Cai4Hong Li5Limin Rong6Gang‐Biao Jiang7Bin Liu8Department of Spine Surgery The Third Affiliated Hospital of Sun Yat‐Sen University Guangzhou 510630 ChinaKey Laboratory for Biobased Materials and Energy of Ministry of Education College of Materials and Energy South China Agricultural University Guangzhou 510642 ChinaDepartment of Spine Surgery The Third Affiliated Hospital of Sun Yat‐Sen University Guangzhou 510630 ChinaKey Laboratory for Biobased Materials and Energy of Ministry of Education College of Materials and Energy South China Agricultural University Guangzhou 510642 ChinaDepartment of Spine Surgery The Third Affiliated Hospital of Sun Yat‐Sen University Guangzhou 510630 ChinaDepartment of Spine Surgery The Third Affiliated Hospital of Sun Yat‐Sen University Guangzhou 510630 ChinaDepartment of Spine Surgery The Third Affiliated Hospital of Sun Yat‐Sen University Guangzhou 510630 ChinaKey Laboratory for Biobased Materials and Energy of Ministry of Education College of Materials and Energy South China Agricultural University Guangzhou 510642 ChinaDepartment of Spine Surgery The Third Affiliated Hospital of Sun Yat‐Sen University Guangzhou 510630 ChinaAbstract In the realm of neural regeneration post‐spinal cord injury, hydrogel scaffolds carrying induced neural stem cells (iNSCs) have demonstrated significant potential. However, challenges such as graft rejection and dysfunction caused by mitochondrial damage persist after transplantation, presenting formidable barriers. Tacrolimus, known for its dual role as an immunosuppressant and promoter of neural regeneration, holds the potential for enhancing iNSC transplantation. However, systemic administration of tacrolimus often comes with severe side effects. This study pioneers the development of a self‐healing hydrogel with sustained‐release tacrolimus (COCu‐Tac), tailored specifically for iNSC transplantation after spinal cord injury. This research reveals that the sustained release of tacrolimus enhances axonal growth and improves mitochondrial quality control in iNSCs and neurons. Further analysis shows that tacrolimus targets FKBP52 rather than FKBP51, enhancing mitophagy via the FKBP52/AKT pathway. This advanced system demonstrates significant efficacy in promoting neural regeneration and restoring motor function following spinal cord injury.https://doi.org/10.1002/advs.202407757FKBP52induced neural stem cellsmitophagyself‐healing hydrogelspinal cord injury |
| spellingShingle | Zhenming Tian Han‐Jian Hu Chun Cheung Chan Tian Hu Chaoyang Cai Hong Li Limin Rong Gang‐Biao Jiang Bin Liu Self‐Healing COCu‐Tac Hydrogel Enhances iNSCs Transplantation for Spinal Cord Injury by Promoting Mitophagy via the FKBP52/AKT Pathway Advanced Science FKBP52 induced neural stem cells mitophagy self‐healing hydrogel spinal cord injury |
| title | Self‐Healing COCu‐Tac Hydrogel Enhances iNSCs Transplantation for Spinal Cord Injury by Promoting Mitophagy via the FKBP52/AKT Pathway |
| title_full | Self‐Healing COCu‐Tac Hydrogel Enhances iNSCs Transplantation for Spinal Cord Injury by Promoting Mitophagy via the FKBP52/AKT Pathway |
| title_fullStr | Self‐Healing COCu‐Tac Hydrogel Enhances iNSCs Transplantation for Spinal Cord Injury by Promoting Mitophagy via the FKBP52/AKT Pathway |
| title_full_unstemmed | Self‐Healing COCu‐Tac Hydrogel Enhances iNSCs Transplantation for Spinal Cord Injury by Promoting Mitophagy via the FKBP52/AKT Pathway |
| title_short | Self‐Healing COCu‐Tac Hydrogel Enhances iNSCs Transplantation for Spinal Cord Injury by Promoting Mitophagy via the FKBP52/AKT Pathway |
| title_sort | self healing cocu tac hydrogel enhances inscs transplantation for spinal cord injury by promoting mitophagy via the fkbp52 akt pathway |
| topic | FKBP52 induced neural stem cells mitophagy self‐healing hydrogel spinal cord injury |
| url | https://doi.org/10.1002/advs.202407757 |
| work_keys_str_mv | AT zhenmingtian selfhealingcocutachydrogelenhancesinscstransplantationforspinalcordinjurybypromotingmitophagyviathefkbp52aktpathway AT hanjianhu selfhealingcocutachydrogelenhancesinscstransplantationforspinalcordinjurybypromotingmitophagyviathefkbp52aktpathway AT chuncheungchan selfhealingcocutachydrogelenhancesinscstransplantationforspinalcordinjurybypromotingmitophagyviathefkbp52aktpathway AT tianhu selfhealingcocutachydrogelenhancesinscstransplantationforspinalcordinjurybypromotingmitophagyviathefkbp52aktpathway AT chaoyangcai selfhealingcocutachydrogelenhancesinscstransplantationforspinalcordinjurybypromotingmitophagyviathefkbp52aktpathway AT hongli selfhealingcocutachydrogelenhancesinscstransplantationforspinalcordinjurybypromotingmitophagyviathefkbp52aktpathway AT liminrong selfhealingcocutachydrogelenhancesinscstransplantationforspinalcordinjurybypromotingmitophagyviathefkbp52aktpathway AT gangbiaojiang selfhealingcocutachydrogelenhancesinscstransplantationforspinalcordinjurybypromotingmitophagyviathefkbp52aktpathway AT binliu selfhealingcocutachydrogelenhancesinscstransplantationforspinalcordinjurybypromotingmitophagyviathefkbp52aktpathway |