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了解椎间盘退变的分子生物学和潜在的基因治疗再生策略:综述。

Understanding the molecular biology of intervertebral disc degeneration and potential gene therapy strategies for regeneration: a review.

机构信息

Sunshine Medical Academy for Research and Training (SMART), Sunshine Hospitals, Secunderabad, Telangana, 500003, India.

出版信息

Gene Ther. 2018 Apr;25(2):67-82. doi: 10.1038/s41434-018-0004-0. Epub 2018 Mar 22.

Abstract

Intervertebral disc degeneration (IVDD) is a multi-factorial process characterized by phenotypic and genotypic changes, which leads to low back pain and disability. Prolonged imbalance between anabolism and catabolism in discs alters their composition resulting in progressive loss of proteoglycans and hydration leading to IVDD. The current managements for IVDD are only able to relieve the symptoms but do not address the underlying pathology of degeneration. Researchers have tried to find out differences between the aging and degeneration of the disc. Intense attempts are in progress for identifying the various factors responsible for disc degeneration, as well as strategies for regeneration. Recently biological approaches have gained thrust in the field of IVDD. The present review illustrates the current understanding of intervertebral disc degeneration and aims to put forth recent advancements in regeneration strategies involving different biological therapies such as growth factor, cell, and gene therapy. The potentials and consequences of these therapies are also extensively discussed along with citing the most suitable method, that is, the gene therapy in detail. Initially, gene therapy was mediated by viral vectors but recent progress has enabled researchers to opt for non-virus-mediated gene therapy methods, which ensure that there are no risks of mutagenicity and infection in target cells. With constant efforts, non-virus-mediated gene therapy may prove to be an extremely powerful tool in treatment of IVDD in future.

摘要

椎间盘退变(IVDD)是一种多因素过程,其特征在于表型和基因型的变化,导致下腰痛和残疾。椎间盘中合成代谢和分解代谢之间的长期失衡会改变其组成,导致蛋白聚糖和水合作用的逐渐丧失,从而导致 IVDD。目前针对 IVDD 的治疗方法只能缓解症状,但不能解决退变的根本病理。研究人员试图找出椎间盘老化和退变之间的差异。目前正在积极寻找导致椎间盘退变的各种因素以及再生策略。最近,生物学方法在 IVDD 领域得到了重视。本综述阐述了目前对椎间盘退变的认识,并旨在提出涉及不同生物学治疗的再生策略的最新进展,如生长因子、细胞和基因治疗。还广泛讨论了这些治疗方法的潜力和后果,并详细介绍了最适合的方法,即基因治疗。最初,基因治疗是通过病毒载体介导的,但最近的进展使研究人员能够选择非病毒介导的基因治疗方法,这确保了靶细胞没有突变和感染的风险。通过不断的努力,非病毒介导的基因治疗可能在未来成为治疗 IVDD 的一种极其强大的工具。

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