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表达转化生长因子-β1的转基因软骨细胞:一种治疗关节软骨损伤的革命性疗法?

Genetically modified chondrocytes expressing TGF-β1: a revolutionary treatment for articular cartilage damage?

作者信息

Elmallah Randa K, Cherian Jeffrey J, Jauregui Julio J, Pierce Todd P, Beaver Walter B, Mont Michael A

机构信息

Rubin Institute for Advanced Orthopedics, Sinai Hospital of Baltimore, Center for Joint Preservation and Replacement , 2401 West Belvedere Avenue, Baltimore, MD 21215 , USA +1 410 601 8500 ; +1 410 601 8501 ;

出版信息

Expert Opin Biol Ther. 2015 Mar;15(3):455-64. doi: 10.1517/14712598.2015.1009886. Epub 2015 Feb 3.

Abstract

INTRODUCTION

Currently, joint arthroplasty remains the only definitive management of osteoarthritis, while other treatment modalities only provide temporary and symptomatic relief. The use of genetically engineered chondrocytes is currently undergoing clinical trials. Specifically, it has been designed to induce cartilage growth and differentiation in patients with degenerative arthritis, with the aim to play a curative role in the disease process.

AREAS COVERED

This treatment involves the incorporation of TGF-β1, which has been determined to play an influential role in chondrogenesis and extracellular matrix synthesis. Using genetic manipulation and viral transduction, TGF-β1 is incorporated into human chondrocytes and administered in a minimally invasive fashion directly to the affected joint. Following a database literature search, we evaluated the current evidence on this product and its outcomes. Furthermore, we also briefly reviewed other treatments developed for chondrogenesis and cartilage regeneration for comparison.

EXPERT OPINION

This treatment method has sustained positive effects on functional outcomes and cartilage growth in initial trials. It allows administration in a minimally invasive manner that does not require extended recovery time. Although several treatment modalities are currently under investigation and appear promising, we hope that these effects can be sustained in further studies. Ultimately, we anticipate that the results may be reproducible in many clinical settings and allow us to effectively treat cartilage damage in patients with degenerative arthritis.

摘要

引言

目前,关节置换术仍是骨关节炎唯一的确定性治疗方法,而其他治疗方式仅能提供暂时的症状缓解。基因工程软骨细胞的应用目前正在进行临床试验。具体而言,其设计目的是诱导退行性关节炎患者的软骨生长和分化,以期在疾病进程中发挥治愈作用。

涵盖领域

该治疗方法涉及整合转化生长因子-β1(TGF-β1),已确定其在软骨生成和细胞外基质合成中发挥重要作用。通过基因操作和病毒转导,将TGF-β1整合到人类软骨细胞中,并以微创方式直接注射到受影响的关节。在进行数据库文献检索后,我们评估了关于该产品及其疗效的现有证据。此外,我们还简要回顾了为软骨生成和软骨再生开发的其他治疗方法以供比较。

专家意见

在初步试验中,这种治疗方法对功能结果和软骨生长具有持续的积极影响。它允许以微创方式给药,无需长时间的恢复时间。尽管目前有几种治疗方式正在研究中且前景看好,但我们希望这些效果能在进一步研究中得以维持。最终,我们预计这些结果在许多临床环境中都可重现,并使我们能够有效治疗退行性关节炎患者的软骨损伤。

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