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热敏性碱性成纤维细胞生长因子修饰水凝胶联合牙髓干细胞对脊髓损伤神经炎症的影响

Thermosensitive bFGF-Modified Hydrogel with Dental Pulp Stem Cells on Neuroinflammation of Spinal Cord Injury.

作者信息

Albashari Abdullkhaleg, He Yan, Zhang Yanni, Ali Jihea, Lin Feiou, Zheng Zengming, Zhang Keke, Cao Yanfan, Xu Chun, Luo Lihua, Wang Jianming, Ye Qingsong

机构信息

School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.

Laboratory for Regenerative Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, Hubei 430064, China.

出版信息

ACS Omega. 2020 Jun 25;5(26):16064-16075. doi: 10.1021/acsomega.0c01379. eCollection 2020 Jul 7.

Abstract

Acute spinal cord injury (SCI) induces severe neuroinflammation, which increases intermediary filaments and neurodegeneration. Previous studies have shown that a basic fibroblast growth factor (bFGF) and dental pulp stem cells (DPSCs) contribute to a protective effect on injured neuronal cells, but the mechanism of SCI repair is still unclear. In this study, in situ heparin (HeP) hydrogel injection containing bFGF and DPSCs (HeP-bFGF-DPSCs), as well as in vitro studies of bFGF and DPSCs, proved an effective control over inflammation. The in vivo application of HeP-bFGF-DPSCs regulated inflammatory reactions and accelerated the nerve regeneration through microtubule stabilization and tissue vasculature. Our mechanistic investigation also showed that bFGF-DPSCs treatment inhibited microglia/macrophage proliferation and activation. Furthermore, HeP-bFGF-DPSCs prevented microglia/macrophage activation and reduced proinflammatory cytokine release. In this paper, we discovered that bFGF and DPSCs worked together to attenuate tissue inflammation of the injured spinal cord, resulting in a superior nerve repair. Our results indicated that a thermosensitive hydrogel delivering bFGF and DPSCs could serve as a promising treatment option for spinal cord injuries.

摘要

急性脊髓损伤(SCI)会引发严重的神经炎症,从而增加中间丝并导致神经退行性变。先前的研究表明,碱性成纤维细胞生长因子(bFGF)和牙髓干细胞(DPSCs)对受损神经元细胞具有保护作用,但SCI修复的机制仍不清楚。在本研究中,含有bFGF和DPSCs的原位肝素(HeP)水凝胶注射剂(HeP-bFGF-DPSCs),以及bFGF和DPSCs的体外研究,证明了对炎症的有效控制。HeP-bFGF-DPSCs的体内应用通过微管稳定和组织血管系统调节炎症反应并加速神经再生。我们的机制研究还表明,bFGF-DPSCs治疗可抑制小胶质细胞/巨噬细胞的增殖和活化。此外,HeP-bFGF-DPSCs可防止小胶质细胞/巨噬细胞活化并减少促炎细胞因子的释放。在本文中,我们发现bFGF和DPSCs共同作用可减轻脊髓损伤部位的组织炎症,从而实现更好的神经修复。我们的结果表明,递送bFGF和DPSCs的热敏水凝胶可能是治疗脊髓损伤的一种有前景的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7049/7346236/4350f61e82d4/ao0c01379_0001.jpg

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