A vascular endothelial growth factor–loaded chitosan-hyaluronic acid hydrogel scaffold enhances the therapeutic effect of adipose-derived stem cells in the context of stroke
Adipose-derived stem cell, one type of mesenchymal stem cells, is a promising approach in treating ischemia-reperfusion injury caused by occlusion of the middle cerebral artery. However, its application has been limited by the complexities of the ischemic microenvironment. Hydrogel scaffolds, which...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2025-12-01
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| Series: | Neural Regeneration Research |
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| Online Access: | https://journals.lww.com/10.4103/NRR.NRR-D-24-00129 |
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| author | Zhijian Zheng Xiaohui Lin Zijun Zhao Qiang Lin Ji Liu Manli Chen Wenwen Wu Zhiyun Wu Nan Liu Hongbin Chen |
| author_facet | Zhijian Zheng Xiaohui Lin Zijun Zhao Qiang Lin Ji Liu Manli Chen Wenwen Wu Zhiyun Wu Nan Liu Hongbin Chen |
| author_sort | Zhijian Zheng |
| collection | DOAJ |
| description | Adipose-derived stem cell, one type of mesenchymal stem cells, is a promising approach in treating ischemia-reperfusion injury caused by occlusion of the middle cerebral artery. However, its application has been limited by the complexities of the ischemic microenvironment. Hydrogel scaffolds, which are composed of hyaluronic acid and chitosan, exhibit excellent biocompatibility and biodegradability, making them promising candidates as cell carriers. Vascular endothelial growth factor is a crucial regulatory factor for stem cells. Both hyaluronic acid and chitosan have the potential to make the microenvironment more hospitable to transplanted stem cells, thereby enhancing the therapeutic effect of mesenchymal stem cell transplantation in the context of stroke. Here, we found that vascular endothelial growth factor significantly improved the activity and paracrine function of adipose-derived stem cells. Subsequently, we developed a chitosan-hyaluronic acid hydrogel scaffold that incorporated vascular endothelial growth factor and first injected the scaffold into an animal model of cerebral ischemia-reperfusion injury. When loaded with adipose-derived stem cells, this vascular endothelial growth factor–loaded scaffold markedly reduced neuronal apoptosis caused by oxygen-glucose deprivation/reoxygenation and substantially restored mitochondrial membrane potential and axon morphology. Further in vivo experiments revealed that this vascular endothelial growth factor–loaded hydrogel scaffold facilitated the transplantation of adipose-derived stem cells, leading to a reduction in infarct volume and neuronal apoptosis in a rat model of stroke induced by transient middle cerebral artery occlusion. It also helped maintain mitochondrial integrity and axonal morphology, greatly improving rat motor function and angiogenesis. Therefore, utilizing a hydrogel scaffold loaded with vascular endothelial growth factor as a stem cell delivery system can mitigate the adverse effects of ischemic microenvironment on transplanted stem cells and enhance the therapeutic effect of stem cells in the context of stroke. |
| format | Article |
| id | doaj-art-2d64f86a2bec487b9b32e02f39d257c4 |
| institution | Kabale University |
| issn | 1673-5374 1876-7958 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj-art-2d64f86a2bec487b9b32e02f39d257c42025-02-06T09:58:39ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53741876-79582025-12-0120123591360510.4103/NRR.NRR-D-24-00129A vascular endothelial growth factor–loaded chitosan-hyaluronic acid hydrogel scaffold enhances the therapeutic effect of adipose-derived stem cells in the context of strokeZhijian ZhengXiaohui LinZijun ZhaoQiang LinJi LiuManli ChenWenwen WuZhiyun WuNan LiuHongbin ChenAdipose-derived stem cell, one type of mesenchymal stem cells, is a promising approach in treating ischemia-reperfusion injury caused by occlusion of the middle cerebral artery. However, its application has been limited by the complexities of the ischemic microenvironment. Hydrogel scaffolds, which are composed of hyaluronic acid and chitosan, exhibit excellent biocompatibility and biodegradability, making them promising candidates as cell carriers. Vascular endothelial growth factor is a crucial regulatory factor for stem cells. Both hyaluronic acid and chitosan have the potential to make the microenvironment more hospitable to transplanted stem cells, thereby enhancing the therapeutic effect of mesenchymal stem cell transplantation in the context of stroke. Here, we found that vascular endothelial growth factor significantly improved the activity and paracrine function of adipose-derived stem cells. Subsequently, we developed a chitosan-hyaluronic acid hydrogel scaffold that incorporated vascular endothelial growth factor and first injected the scaffold into an animal model of cerebral ischemia-reperfusion injury. When loaded with adipose-derived stem cells, this vascular endothelial growth factor–loaded scaffold markedly reduced neuronal apoptosis caused by oxygen-glucose deprivation/reoxygenation and substantially restored mitochondrial membrane potential and axon morphology. Further in vivo experiments revealed that this vascular endothelial growth factor–loaded hydrogel scaffold facilitated the transplantation of adipose-derived stem cells, leading to a reduction in infarct volume and neuronal apoptosis in a rat model of stroke induced by transient middle cerebral artery occlusion. It also helped maintain mitochondrial integrity and axonal morphology, greatly improving rat motor function and angiogenesis. Therefore, utilizing a hydrogel scaffold loaded with vascular endothelial growth factor as a stem cell delivery system can mitigate the adverse effects of ischemic microenvironment on transplanted stem cells and enhance the therapeutic effect of stem cells in the context of stroke.https://journals.lww.com/10.4103/NRR.NRR-D-24-00129adipose-derived stem cellschitosanhyaluronic acidhydrogelischemia-reperfusionoxygen-glucose deprivation/reoxygenationstroketransient middle cerebral artery occlusiontransplantationvascular endothelial growth factor |
| spellingShingle | Zhijian Zheng Xiaohui Lin Zijun Zhao Qiang Lin Ji Liu Manli Chen Wenwen Wu Zhiyun Wu Nan Liu Hongbin Chen A vascular endothelial growth factor–loaded chitosan-hyaluronic acid hydrogel scaffold enhances the therapeutic effect of adipose-derived stem cells in the context of stroke Neural Regeneration Research adipose-derived stem cells chitosan hyaluronic acid hydrogel ischemia-reperfusion oxygen-glucose deprivation/reoxygenation stroke transient middle cerebral artery occlusion transplantation vascular endothelial growth factor |
| title | A vascular endothelial growth factor–loaded chitosan-hyaluronic acid hydrogel scaffold enhances the therapeutic effect of adipose-derived stem cells in the context of stroke |
| title_full | A vascular endothelial growth factor–loaded chitosan-hyaluronic acid hydrogel scaffold enhances the therapeutic effect of adipose-derived stem cells in the context of stroke |
| title_fullStr | A vascular endothelial growth factor–loaded chitosan-hyaluronic acid hydrogel scaffold enhances the therapeutic effect of adipose-derived stem cells in the context of stroke |
| title_full_unstemmed | A vascular endothelial growth factor–loaded chitosan-hyaluronic acid hydrogel scaffold enhances the therapeutic effect of adipose-derived stem cells in the context of stroke |
| title_short | A vascular endothelial growth factor–loaded chitosan-hyaluronic acid hydrogel scaffold enhances the therapeutic effect of adipose-derived stem cells in the context of stroke |
| title_sort | vascular endothelial growth factor loaded chitosan hyaluronic acid hydrogel scaffold enhances the therapeutic effect of adipose derived stem cells in the context of stroke |
| topic | adipose-derived stem cells chitosan hyaluronic acid hydrogel ischemia-reperfusion oxygen-glucose deprivation/reoxygenation stroke transient middle cerebral artery occlusion transplantation vascular endothelial growth factor |
| url | https://journals.lww.com/10.4103/NRR.NRR-D-24-00129 |
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