Graft of the NT-3 persistent delivery gelatin sponge scaffold promotes axon regeneration, attenuates inflammation, and induces cell migration in rat and canine with spinal cord injury

Graft of the NT-3 persistent delivery gelatin sponge scaffold promotes axon regeneration, attenuates inflammation, and induces cell migration in rat and canine with spinal cord injury
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NT-3持久递送明胶海绵支架的移植物促进轴突再生,减轻炎症,并诱导脊髓损伤大鼠和犬的细胞迁移

DOI:
10.1016/j.biomaterials.2015.11.059
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发表时间:
2016-03-01
期刊:
影响因子:
14
通讯作者:
Zeng, Yuan-Shan
Zeng, Yuan-Shan
中科院分区:
工程技术1区
文献类型:
--
作者:
Li, Ge;Che, Ming-Tian;Zeng, Yuan-Shan

文献摘要

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持续的神经营养因子递送对于在脊髓损伤(SCI)中创造细胞存活和神经再生的微环境至关重要。本研究旨在开发一种NT-3/丝素蛋白涂层明胶海绵支架(NF-GS)作为一种新型的人工控释治疗SCI的方法。在体外,将骨髓间充质干细胞(MSCs)植入NF -GS中,释放试验表明NF -GS能够产生长达28天的持续释放NT-3。NF-GS中的MSCs具有较高的细胞活性,细胞分布和表型良好.将其移植于大鼠和犬脊髓损伤部位,移植后表现出较强的生物相容性。移植后4周,NT-3浓度明显高于对照组。损伤/移植部位的空腔面积由于组织再生和与髓鞘相关的轴突延伸通过神经胶质瘢痕进入NF-GS而显著减少。此外,NF-GS通过减少CD 68阳性细胞和TNF-α来减轻炎症。一个显著的特征是出现了一些细胞和髓磷脂样结构,这些细胞和结构似乎穿过NF -GS。目前的结果表明,NF-GS具有控制NT-3从NT-3/丝素蛋白复合物中释放的特性,从而促进损伤的脊髓的再生。(C)2015爱思唯尔有限公司版权所有。
Persistent neurotrophic factor delivery is crucial to create a microenvironment for cell survival and nerve regeneration in spinal cord injury (SCI). This study aimed to develop a NT-3/fibroin coated gelatin sponge scaffold (NF-GS) as a novel controlled artificial release therapy for SCI. In vitro, bone marrow -derived mesenchymal stem cells (MSCs) were planted into the NF -GS and release test showed that NF -GS was capable to generate a sustainable NT-3 release up to 28 days. MSCs in NF -GS had high cell activity with excellent cell distribution and phenotype. Then, the NF -GS was transplanted into the injury site of spinal cord of rat and canine in vivo, which exhibited strong biocompatibility during post -transplantation period. Four weeks following transplantation, the concentration of NT-3 was much higher than that in control groups. Cavity areas in the injury/graft site were significantly reduced due to tissue regeneration and axonal extensions associated with myelin sheath through the glial scar into the NF -GS. Additionally, the NF -GS decreased the inflammation by reducing the CD68 positive cells and TNF-alpha. A striking feature was the occurrence of some cells and myelin -like structure that appeared to traverse the NF -GS. The present results demonstrate that the NF -GS has the property to control the release of NT-3 from the NT-3/fibroin complex thus facilitating regeneration of injured spinal cord. (C) 2015 Elsevier Ltd. All rights reserved.