Maidhof Robert, Alipui D Olivier, Rafiuddin Asfi, Levine Mitchell, Grande Daniel A, Chahine Nadeen O
The Feinstein Institute for Medical Research, Hofstra North Shore LIJ School of Medicine, Manhasset, New York 11030, USA.
Discov Med. 2012 Dec;14(79):401-11.
Intervertebral disc disease is characterized by a series of deleterious changes in cellularity that lead to loss of extracellular matrix structure, altered biomechanical loading, and symptomatic pain. At present the "gold standard" of therapy is discectomy -- surgical removal of the diseased disc followed by fusion of the adjacent vertebral bodies. The procedure alleviates pain, but fusion limits range of motion and alters the mechanical loading at other spinal levels, hastening disease at previously unaffected sites. Biological therapeutics have the potential to repair damaged tissue by several means: (1) altering cell phenotype to regenerate matrix components, (2) augmenting tissue with reparative cells, (3) delivering bioactive materials to reestablish disc biomechanics and serve as a template for cell-based regeneration. Although research into biological treatments for disc degeneration has been ongoing for over a decade, few treatments have progressed to clinical testing and none are currently commercially available, primarily due to a limited understanding of disease etiology. Further work is needed to identify targets and interventional time points as disc degeneration progresses from early to later stages. This review focuses on emerging trends in biological treatments and identifies key obstacles to their clinical translation.
椎间盘疾病的特征是细胞数量发生一系列有害变化,导致细胞外基质结构丧失、生物力学负荷改变以及出现疼痛症状。目前,治疗的“金标准”是椎间盘切除术——手术切除患病椎间盘,然后融合相邻椎体。该手术可缓解疼痛,但融合会限制活动范围,并改变其他脊柱节段的机械负荷,加速先前未受影响部位的疾病发展。生物疗法有潜力通过多种方式修复受损组织:(1)改变细胞表型以再生基质成分;(2)用修复细胞增强组织;(3)递送生物活性材料以重建椎间盘生物力学,并作为基于细胞的再生模板。尽管对椎间盘退变的生物治疗研究已经进行了十多年,但很少有治疗方法进入临床试验阶段,目前也没有一种疗法可供商业使用,主要原因是对疾病病因的了解有限。随着椎间盘退变从早期发展到后期,需要进一步开展工作以确定靶点和干预时间点。本综述重点关注生物治疗的新趋势,并确定其临床转化的关键障碍。