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负载活化雪旺细胞的甲基丙烯酰化明胶水凝胶支架可减轻脊髓损伤后的细胞凋亡并促进功能恢复。

Gelatin methacryloyl hydrogel scaffold loaded with activated Schwann cells attenuates apoptosis and promotes functional recovery following spinal cord injury.

作者信息

Liu Yang, Yu Hao, Yu Peng, Peng Peng, Li Chao, Xiang Zhenyang, Ban Dexiang

机构信息

Department of Orthopedics, Tianjin Medical University General Hospital, Heping, Tianjin 300052, P.R. China.

International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, Heping, Tianjin 300052, P.R. China.

出版信息

Exp Ther Med. 2023 Feb 15;25(4):144. doi: 10.3892/etm.2023.11843. eCollection 2023 Apr.

DOI:10.3892/etm.2023.11843
PMID:36911380
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9995797/
Abstract

Spinal cord injury (SCI) is a refractory disease of the central nervous system with a high disability and incidence rate. In recent years, bioactive material combined with cell transplantation has been considered an effective method for the treatment of SCI. The present study encapsulated activated Schwann cells (ASCs) in a 3D gelatin methacryloyl (GelMA) hydrogel in order to investigate its therapeutic effects on SCI. ASCs were isolated from previously ligated rat sciatic nerves. Scanning electron microscopy and live/dead staining were used to evaluate the biocompatibility of hydrogels with the ASCs. The scaffold was transplanted into the spinal cord of rats in the hemisection model. Behavioral tests and hematoxylin and eosin staining were employed to assess the locomotion recovery and lesion areas before and after treatment. Cell apoptosis was evaluated using TUNEL staining and immunochemistry, and apoptosis-related protein expression was detected using western blot analysis. The ASCs exhibited a favorable survival and proliferative ability in the 3D GelMA hydrogel. The scaffold transplantation significantly reduced the cavities and improved functional recovery. Moreover, the GelMA/ASCs implants significantly inhibited cell apoptosis following SCI and this effect may be mediated via the p38 MAPK pathway. Overall, these findings indicated that ASCs combined with the 3D GelMA hydrogel may be a promising therapeutic strategy for SCI.

摘要

脊髓损伤(SCI)是一种中枢神经系统难治性疾病,致残率和发病率都很高。近年来,生物活性材料联合细胞移植被认为是治疗SCI的有效方法。本研究将活化雪旺细胞(ASCs)封装在三维甲基丙烯酰化明胶(GelMA)水凝胶中,以研究其对SCI的治疗效果。ASCs从先前结扎的大鼠坐骨神经中分离出来。采用扫描电子显微镜和活/死染色法评估水凝胶与ASCs的生物相容性。将支架移植到半横断模型大鼠的脊髓中。采用行为学测试和苏木精-伊红染色评估治疗前后的运动恢复情况和损伤区域。使用TUNEL染色和免疫化学评估细胞凋亡,并通过蛋白质免疫印迹分析检测凋亡相关蛋白表达。ASCs在三维GelMA水凝胶中表现出良好的存活和增殖能力。支架移植显著减少了空洞并改善了功能恢复。此外,GelMA/ASCs植入物显著抑制了SCI后的细胞凋亡,这种作用可能是通过p38丝裂原活化蛋白激酶(MAPK)途径介导的。总体而言,这些研究结果表明,ASCs联合三维GelMA水凝胶可能是一种有前景的SCI治疗策略。

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本文引用的文献

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Human Schwann Cell Transplantation for Spinal Cord Injury: Prospects and Challenges in Translational Medicine.人雪旺细胞移植治疗脊髓损伤:转化医学中的前景与挑战
Front Cell Neurosci. 2021 Jun 18;15:690894. doi: 10.3389/fncel.2021.690894. eCollection 2021.
2
Promoting 3D neuronal differentiation in hydrogel for spinal cord regeneration.促进水凝胶中的 3D 神经元分化以实现脊髓再生。
Colloids Surf B Biointerfaces. 2020 Oct;194:111214. doi: 10.1016/j.colsurfb.2020.111214. Epub 2020 Jun 24.
3
Designer, injectable gels to prevent transplanted Schwann cell loss during spinal cord injury therapy.设计用于防止脊髓损伤治疗过程中移植雪旺细胞丢失的可注射凝胶。
Sci Adv. 2020 Apr 1;6(14):eaaz1039. doi: 10.1126/sciadv.aaz1039. eCollection 2020 Apr.
4
Excess administration of miR-340-5p ameliorates spinal cord injury-induced neuroinflammation and apoptosis by modulating the P38-MAPK signaling pathway.过量表达 miR-340-5p 通过调节 P38-MAPK 信号通路改善脊髓损伤诱导的神经炎症和细胞凋亡。
Brain Behav Immun. 2020 Jul;87:531-542. doi: 10.1016/j.bbi.2020.01.025. Epub 2020 Jan 31.
5
Progranulin deficiency exacerbates spinal cord injury by promoting neuroinflammation and cell apoptosis in mice.颗粒蛋白前体缺乏通过促进小鼠脊髓损伤中的神经炎症和细胞凋亡而加重损伤。
J Neuroinflammation. 2019 Nov 27;16(1):238. doi: 10.1186/s12974-019-1630-1.
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Cell Therapeutic Strategies for Spinal Cord Injury.脊髓损伤的细胞治疗策略
Adv Wound Care (New Rochelle). 2019 Nov 1;8(11):585-605. doi: 10.1089/wound.2019.1046. Epub 2019 Oct 16.
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