Mechanisms of Action

1. Immunomodulation and Anti-Inflammation
   MSCs secrete anti-inflammatory cytokines (e.g., IL-10, TGF-β) and polarize macrophages toward the M2 phenotype, thereby suppressing chronic intradiscal inflammation and creating a pro-regenerative environment.

2. Matrix Regeneration
   Injected MSCs and their secretome stimulate nucleus pulposus (NP) cells to produce collagen II and proteoglycans, partially restoring water content, elasticity, and disc height.

3. Neuroprotection and Pain Modulation
   MSCs release neurotrophic factors such as BDNF and HGF, which protect against apoptosis, support neuronal survival, and may reduce radicular pain via modulation of nociceptive signaling.

4. Exosome/Paracrine Effects
   Increasing evidence suggests that the regenerative benefits are mediated mainly by exosomes and soluble factors rather than direct long-term engraftment, explaining why even low-dose intradiscal injections can achieve clinical benefits.

Clinical Outcomes in Humans

• Pain Reduction
  Multiple early-phase clinical trials have shown significant reductions in Visual Analog Scale (VAS) pain scores after intradiscal MSC injections, with effects sustained up to 12–24 months in some cohorts.

• Functional Improvement
  Improvements in Oswestry Disability Index (ODI) and patient-reported quality-of-life measures have been consistently reported in small randomized and uncontrolled trials.

• Radiological Evidence
  MRI follow-ups in some studies demonstrated partial recovery of T2 signal intensity and stabilization of disc height, suggesting structural benefits alongside symptom relief.

• Long-Term Follow-Up
  Systematic reviews highlight that clinical benefits (pain and function) are generally sustained at 12 months or longer, though heterogeneity in study design and limited sample sizes remain barriers to definitive conclusions.

Safety Profile

Across Phase I/II trials, intradiscal MSC therapy has demonstrated a favorable safety profile. Most adverse events were mild, such as transient post-injection pain. Serious complications—such as infection, ectopic tissue formation, or tumorigenesis—have been extremely rare. Nonetheless, experts emphasize that treatment should currently remain within controlled clinical trials or regulated medical centers.

Key Human Studies and Reviews

• Xie et al. (2021): Systematic review/meta-analysis demonstrated significant reductions in VAS and ODI after MSC therapy.

• Kumar et al. (2017): Phase I trial confirmed safety and tolerability of combined MSC and HA intradiscal injection.

• Lee et al. (2023): Phase I trial using MSCs with hyaluronic acid reported clinical improvement with no major adverse events.

• Pers et al. (2024): Phase II allogeneic bone marrow MSC study showed clinical benefit in discogenic pain patients.

Conclusion

Stem cell–based therapies, especially MSCs, represent a promising regenerative strategy for degenerative disc disease. Human clinical studies have demonstrated meaningful reductions in pain, functional recovery, and radiological stabilization, with a reassuring safety profile. While results are encouraging, the field still requires large, randomized, long-term trials to define the optimal cell source, dosage, and patient selection criteria. Until then, MSC therapy for DDD should be pursued under controlled research protocols.

干细胞治疗退行性椎间盘疾病（DDD）：作用机制、临床疗效与人类证据

概述

退行性椎间盘疾病（DDD）是导致慢性腰痛和功能障碍的主要原因之一。传统治疗方式——包括止痛药、物理治疗以及脊柱融合手术——主要以缓解症状为主，难以逆转椎间盘退变。近年来，基于干细胞的疗法，特别是间充质干细胞（MSCs），在缓解疼痛、改善功能、以及潜在促进椎间盘组织再生方面显示出临床应用的前景。

作用机制

1. 免疫调节与抗炎作用
   MSCs 能分泌抗炎性细胞因子（如 IL-10、TGF-β），并诱导巨噬细胞向 M2 表型转化，从而抑制椎间盘内的慢性炎症，营造有利于修复的微环境。

2. 基质再生
   注射入椎间盘的 MSCs 及其分泌产物能够刺激髓核细胞合成Ⅱ型胶原和蛋白聚糖，部分恢复水分含量和弹性，从而帮助维持或恢复椎间隙高度。

3. 神经营养与镇痛调节
   MSCs 可释放神经营养因子（如 BDNF、HGF），减少细胞凋亡，支持神经元存活，并可能通过调控痛觉信号传导降低根性神经痛。

4. 外泌体与旁分泌效应
   越来越多的研究提示，MSCs 的主要作用并非长期存活分化，而是通过外泌体与可溶性因子实现免疫调节与基质修复，这也解释了低剂量椎间盘注射即可带来疗效的现象。

人体临床结果

• 疼痛缓解
  多项早期临床试验显示，椎间盘内注射 MSCs 可显著降低患者的视觉模拟疼痛评分（VAS），部分病例的疗效可持续 12–24 个月。

• 功能改善
  多个随机对照或单臂研究一致报道，患者的 Oswestry 功能障碍指数（ODI）及生活质量评分明显改善。

• 影像学证据
  MRI 随访显示部分患者椎间盘 T2 信号强度增加，椎间隙高度稳定或恢复，提示在症状缓解之外可能存在结构性获益。

• 长期随访
  系统性回顾表明，临床获益（疼痛与功能改善）一般可维持超过 12 个月，但受限于研究样本量和设计差异，目前结论仍需进一步大规模试验证实。

安全性

在 I/II 期临床试验中，椎间盘内 MSC 治疗展现出良好的安全性。常见不良反应多为轻度，如注射部位疼痛短暂加重。严重并发症（如感染、异位组织形成或肿瘤风险）极为罕见。研究者普遍建议，该治疗目前应主要在受控临床试验或合格医疗中心内进行。