Thermos-responsive hydrogel system encapsulated engineered exosomes attenuate inflammation and oxidative damage in acute spinal cord injury
Introduction: Spinal cord injury (SCI) is a serious and disabling condition, and the effectiveness of conventional treatment is limited, such as supportive treatment and emergency surgery. Exosomes derived from umbilical cord mesenchymal stem cells (UCMSC-Exos) have potential therapeutic effects on...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-08-01
|
| Series: | Frontiers in Bioengineering and Biotechnology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1216878/full |
| _version_ | 1797751879053082624 |
|---|---|
| author | Yu Xiao Xinmei Hu Peng Jiang Zhongquan Qi |
| author_facet | Yu Xiao Xinmei Hu Peng Jiang Zhongquan Qi |
| author_sort | Yu Xiao |
| collection | DOAJ |
| description | Introduction: Spinal cord injury (SCI) is a serious and disabling condition, and the effectiveness of conventional treatment is limited, such as supportive treatment and emergency surgery. Exosomes derived from umbilical cord mesenchymal stem cells (UCMSC-Exos) have potential therapeutic effects on SCI but are limited by delivery efficiency. Our study aimed to further investigate the therapeutic effects of miR-138-modified UCMSC-exosomes (Exos-138) following SCI.Methods: We developed an injectable triblock polymer of polyglycolic acid copolymer and polyethylene glycol (PLGA-PEG-PLGA)-loaded temperature-sensitive hydrogel of miR-138-modified stem cell exosomes and characterised its biocompatibility in vitro. In Sprague-Dawley rats with SCI, the hydrogel was injected into the injury site, behavioural scores were measured, and pathological analysis was conducted postoperatively to assess neurological recovery.Results:In vitro, our data demonstrated that miR-138-5p-modified UCMSC-Exos can reduce inflammation levels in BV-2 cells through the NLRP3-caspase1 signalling pathway and reduce neuronal apoptosis by downregulating intracellular reactive oxygen species levels through the Nrf2-keap1 signalling cascade. The results of in vivo experiments showed that the P-Exos-138 hydrogel promoted neurological recovery in rats with SCI.Discussion: Our study explored a novel exosome delivery system that can be a potential therapeutic strategy for SCI. Our study, currently, has theoretical value; however, it can serve as a basis for further investigations on the treatment approaches at various stages of SCI development in inflammation-dependent injury of the central nervous system. |
| first_indexed | 2024-03-12T16:55:03Z |
| format | Article |
| id | doaj.art-cf53007120214fd3ac794eadcdd378dc |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-03-12T16:55:03Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-cf53007120214fd3ac794eadcdd378dc2023-08-08T09:18:08ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852023-08-011110.3389/fbioe.2023.12168781216878Thermos-responsive hydrogel system encapsulated engineered exosomes attenuate inflammation and oxidative damage in acute spinal cord injuryYu XiaoXinmei HuPeng JiangZhongquan QiIntroduction: Spinal cord injury (SCI) is a serious and disabling condition, and the effectiveness of conventional treatment is limited, such as supportive treatment and emergency surgery. Exosomes derived from umbilical cord mesenchymal stem cells (UCMSC-Exos) have potential therapeutic effects on SCI but are limited by delivery efficiency. Our study aimed to further investigate the therapeutic effects of miR-138-modified UCMSC-exosomes (Exos-138) following SCI.Methods: We developed an injectable triblock polymer of polyglycolic acid copolymer and polyethylene glycol (PLGA-PEG-PLGA)-loaded temperature-sensitive hydrogel of miR-138-modified stem cell exosomes and characterised its biocompatibility in vitro. In Sprague-Dawley rats with SCI, the hydrogel was injected into the injury site, behavioural scores were measured, and pathological analysis was conducted postoperatively to assess neurological recovery.Results:In vitro, our data demonstrated that miR-138-5p-modified UCMSC-Exos can reduce inflammation levels in BV-2 cells through the NLRP3-caspase1 signalling pathway and reduce neuronal apoptosis by downregulating intracellular reactive oxygen species levels through the Nrf2-keap1 signalling cascade. The results of in vivo experiments showed that the P-Exos-138 hydrogel promoted neurological recovery in rats with SCI.Discussion: Our study explored a novel exosome delivery system that can be a potential therapeutic strategy for SCI. Our study, currently, has theoretical value; however, it can serve as a basis for further investigations on the treatment approaches at various stages of SCI development in inflammation-dependent injury of the central nervous system.https://www.frontiersin.org/articles/10.3389/fbioe.2023.1216878/fullexosomesPLGA-PEG-PLGAmiR-138-5pNLRP3Nrf2SCI |
| spellingShingle | Yu Xiao Xinmei Hu Peng Jiang Zhongquan Qi Thermos-responsive hydrogel system encapsulated engineered exosomes attenuate inflammation and oxidative damage in acute spinal cord injury Frontiers in Bioengineering and Biotechnology exosomes PLGA-PEG-PLGA miR-138-5p NLRP3 Nrf2 SCI |
| title | Thermos-responsive hydrogel system encapsulated engineered exosomes attenuate inflammation and oxidative damage in acute spinal cord injury |
| title_full | Thermos-responsive hydrogel system encapsulated engineered exosomes attenuate inflammation and oxidative damage in acute spinal cord injury |
| title_fullStr | Thermos-responsive hydrogel system encapsulated engineered exosomes attenuate inflammation and oxidative damage in acute spinal cord injury |
| title_full_unstemmed | Thermos-responsive hydrogel system encapsulated engineered exosomes attenuate inflammation and oxidative damage in acute spinal cord injury |
| title_short | Thermos-responsive hydrogel system encapsulated engineered exosomes attenuate inflammation and oxidative damage in acute spinal cord injury |
| title_sort | thermos responsive hydrogel system encapsulated engineered exosomes attenuate inflammation and oxidative damage in acute spinal cord injury |
| topic | exosomes PLGA-PEG-PLGA miR-138-5p NLRP3 Nrf2 SCI |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1216878/full |
| work_keys_str_mv | AT yuxiao thermosresponsivehydrogelsystemencapsulatedengineeredexosomesattenuateinflammationandoxidativedamageinacutespinalcordinjury AT xinmeihu thermosresponsivehydrogelsystemencapsulatedengineeredexosomesattenuateinflammationandoxidativedamageinacutespinalcordinjury AT pengjiang thermosresponsivehydrogelsystemencapsulatedengineeredexosomesattenuateinflammationandoxidativedamageinacutespinalcordinjury AT zhongquanqi thermosresponsivehydrogelsystemencapsulatedengineeredexosomesattenuateinflammationandoxidativedamageinacutespinalcordinjury |