Autologous mesenchymal stem/stromal Cells for the Treatment of workers affected by chronic low back pain due to multilevel InterVErtebral disc degeneration: a phase IIB randomized clinical trial

Background: Low Back pain is a highly prevalent disabling condition in the general population. It is estimated that 50-80% of adults have experienced at least one painful episode in their lifetime. It can be associated with physically demanding jobs, as well as sedentary occupations, low levels of physical activity. The degeneration of the intervertebral disc is recognized as one of the most significant causes of low back pain. Degenerated discs thus have a lower water content than normal discs and, when under load, lose height and fluid more rapidly. Intervertebral disc degeneration (IDD) involves a progressive decrease in healthy resident cells, with catabolic processes prevailing over tissue anabolism. Stem cells, due to their self-renewal, low immunogenicity, and presence in various tissues, are used to treat numerous diseases, including IDD. In IDD treatment, mesenchymal stem cells (MSCs), intervertebral disc stem cells (IVDSCs), and pluripotent stem cells (PSCs) are commonly utilized. They help slow down IDD by synthesizing new extracellular matrix (ECM), secreting growth factors and anti-inflammatory substances, and improving the mechanical properties of nucleus pulposus (NP) cells. Aim: To evaluate the efficacy of intradiscal injection of autologous BM-MSCs in workers affected by chronic LBP, due to multilevel (max. 4 levels) lumbar IDD, after 12 months of treatment in terms of pain relief (VAS), functionality (ODI), quality of life (SF-36), and work ability index (WAI). Secondary objective is to assess safety and tolerability of the treatment Material and method: this is a phase 2b efficacy monocenter, prospective, randomized, controlled double blinded trial, comparing intra-discal autologous adult BM-MSC therapy and sham treated controls in subjects with chronic LBP (> 6 months) due to lumbar multilevel IDD (max. 4 levels) unresponsive to conventional therapy. Treatment allocation was performed online by a central randomization web-service. Patient follow up was performed at 1, 3, 6 and 12 months including clinical parameters and PROMs (VAS, ODI, SF- 36, WAI). The data are presented as mean ± Standard Deviation (SD) and Standard Error (SD). Normality of the data was assessed using the Shapiro-Wilk test. To examine mean differences between preoperative and postoperative 12 months time point, repeated-measures ANOVA was employed. Pairwise comparisons between preoperative and postoperative time points were conducted using the paired sample t-test. All statistical analyses were carried out using SPSS statistical software version 26.0 Results: Fifty-eight patients were enrolled in the clinical study, 44 patients completed the 12-month follow-up visit. Conclusion: This randomized controlled trial (RCT) demonstrated that autologous bone marrow-derived MSC therapy is minimally invasive, effective, and safe, thus supporting further research to validate its clinical utility and long-term effects.