Center of Experimental Rheumatology, University Hospital Zurich and Balgrist University Hospital, University of Zurich, CH-8008 Zurich, Switzerland.
Tissue Engineering for Orthopaedics and Mechanobiology, Bone & Joint Program, Department for BioMedical Research (DBMR), Medical Faculty, University of Bern, CH-3008 Bern, Switzerland.
Int J Mol Sci. 2022 Feb 28;23(5):2721. doi: 10.3390/ijms23052721.
Low back pain (LBP) has been among the leading causes of disability for the past 30 years. This highlights the need for improvement in LBP management. Many clinical trials focus on developing treatments against degenerative disc disease (DDD). The multifactorial etiology of DDD and associated risk factors lead to a heterogeneous patient population. It comes as no surprise that the outcomes of clinical trials on intradiscal mesenchymal stem cell (MSC) injections for patients with DDD are inconsistent. Intradiscal MSC injections have demonstrated substantial pain relief and significant disability-related improvements, yet they have failed to regenerate the intervertebral disc (IVD). Increasing evidence suggests that the positive outcomes in clinical trials might be attributed to the immunomodulatory potential of MSCs rather than to their regenerative properties. Therefore, patient stratification for inflammatory DDD phenotypes may (i) better serve the mechanisms of action of MSCs and (ii) increase the treatment effect. Modic type 1 changes-pathologic inflammatory, fibrotic changes in the vertebral bone marrow-are frequently observed adjacent to degenerated IVDs in chronic LBP patients and represent a clinically distinct subpopulation of patients with DDD. This review discusses whether degenerated IVDs of patients with Modic type 1 changes should be treated with an intradiscal MSC injection.
过去 30 年来,下腰痛(LBP)一直是导致残疾的主要原因之一。这凸显了改善 LBP 管理的必要性。许多临床试验都专注于开发针对退行性椎间盘疾病(DDD)的治疗方法。DDD 的多因素病因和相关危险因素导致患者人群存在异质性。毫不奇怪,针对 DDD 患者椎间盘内间充质干细胞(MSC)注射的临床试验结果不一致。椎间盘内 MSC 注射已证明可显著缓解疼痛并显著改善与残疾相关的问题,但未能再生椎间盘(IVD)。越来越多的证据表明,临床试验中的阳性结果可能归因于 MSC 的免疫调节潜力,而不是其再生特性。因此,对炎症性 DDD 表型的患者进行分层可能会:(i)更好地了解 MSC 的作用机制;(ii)提高治疗效果。Modic 类型 1 改变——椎体骨髓的病理性炎症、纤维性改变——在慢性 LBP 患者的退变 IVD 旁经常观察到,代表了 DDD 患者中具有临床显著差异的亚群。这篇综述讨论了是否应使用椎间盘内 MSC 注射治疗患有 Modic 类型 1 改变的患者的退变 IVD。