摘要
前言:间充质干细胞(MSCs)是神经组织工程的有前途的候选细胞。MSCs分泌的脑源性神经营养因子(BDNF)可促进神经分化减轻炎症反应。基因转染技术是提高细胞因子分泌水平和增强细胞功能的有效策略。然而,转染和环境敏感干细胞的体内基因表达因其安全性和转染效率的要求而成为最具挑战性的研究课题之一。在本研究中,基因Tran本研究在脂质体载体ScreenFectRA的基础上,应用转染技术制备BDNF基因重组MSCs,以提高原位免疫后细胞存活率和基因表达。以透明质酸为载体,构建了一种黏附肽修饰的水凝胶支架。用PPFLMLLKGSTR对支架进行了优化和改性。转染者在体外培养的三维支架中,MSCs的细胞存活率和持续基因表达均有提高。与未转染的MSCs相比,基因重组MSCs有效地改善了spi。Nal组织完整,抑制胶质瘢痕形成,减轻炎症反应。当细胞植入没有支架的情况下,这些效应被发现被贴现。结论:研究开发为治疗严重脊髓损伤提供了一种很有前途的植入系统,为ScreenfectR A在和三维基因表达一样的干细胞治疗神经组织修复中的作用提供了初步认识。
关键词: 基因转染,间充质干细胞,脊髓损伤,脑源性神经营养因子,水凝胶支架,粘附肽。
Current Gene Therapy
Title:Transplantation of BDNF Gene Recombinant Mesenchymal Stem Cells and Adhesive Peptide-modified Hydrogel Scaffold for Spinal Cord Repair
Volume: 18 Issue: 1
关键词: 基因转染,间充质干细胞,脊髓损伤,脑源性神经营养因子,水凝胶支架,粘附肽。
摘要: Introduction: Mesenchymal Stem Cells (MSCs) are promising candidates for nerve tissue engineering. Brain Derived Neurotrophic Factor (BDNF) secreted by MSCs can function to increase neural differentiation and relieve inflammation response. Gene transfection technology is an efficient strategy to increase the secretion levels of cytokines and enhance cellular functions. However, transfection and in vivo gene expression of environmentally sensitive stem cells have been one of the most challenging subjects due to the requirement in both safety and transfection efficiency. In this study, gene transfection technology was applied to prepare BDNF gene recombinant MSCs based on our previously reported liposomal vector ScreenFect® A. To improve cellular survival and gene expression after in situ implantation of MSCs, an adhesive peptide modified hydrogel scaffold was constructed using hyaluronic acid. The scaffold was optimized and modified with an adhesive peptide PPFLMLLKGSTR. The transfected MSCs exhibited improved cellular survival and sustained gene expression in the three-Dimentional (3D) scaffold in vitro. Compared to untransfected MSCs, gene recombinant MSCs effectively improved spinal tissue integrity, inhibited glial scar formation and alleviated inflammatory response. These effects were found discounted when cells were implanted without the scaffold.
Conclusion: The study developed a promising implantation system for therapy of severe spinal cord injury and provided the first understanding of Screenfect® A about its functions on stem cell therapy for nerve tissue repair as well as three-dimentional gene expression.
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Transplantation of BDNF Gene Recombinant Mesenchymal Stem Cells and Adhesive Peptide-modified Hydrogel Scaffold for Spinal Cord Repair, Current Gene Therapy 2018; 18 (1) . https://dx.doi.org/10.2174/1566523218666180413150023
DOI https://dx.doi.org/10.2174/1566523218666180413150023 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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