Intradiscal Injection of Mesenchymal Stem Cells for the Treatment of Low Back Pain: a Pilot Study on a Subgroup of Patients Enrolled in a Double Blind Randomized Clinical Trial

The World Health Organisation has included low back pain (LBP) in its list of priority diseases. Notably, degenerative disc disease (DDD), which is one of the main cause of LBP, presents a large, unmet medical need which results in a disabling loss of mechanical function. Today, no efficient therapy is available. Chronic cases often receive surgery, which may lead to biomechanical problems and accelerated degeneration of adjacent segments. Mesenchymal stem cells-based, regenerative therapies may avoid these issues and provide the world’s first effective therapy for this common and debilitating disease. Indeed, preliminary results are really encouraging. The aim of this pilot study is to assess the efficacy of intradiscal injection of bone marrow mesenchymal stem cells (BM-MSCs) in a subset of patients affected by LBP enrolled at Campus Bio-Medico University. The present study is a prospective, randomized, double blind, phase 2b study comparing allogeneic BM-MSCs with sham controls on a total of 11 patients affected with chronic LBP (lasting for more than 6 months) due to lumbar DDD (grade 3-4 according to Pfirrmann degenerative scale assessed using T2-weighted MRI at one lumbar level from L1 to S1) not responsive to conventional therapy. Clinical visits were performed preoperatively, at 1, 3, 6 and 12 months post-op by also performing the Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), 36-Item Short Form Survey (SF-36) and Work Ability Index (WAI). Disc water and proteoglycan content was assessed pre-operatively, at 6 and 12 months post-op on magnetic resonance imaging (MRI) measured through Pfirmann score grading system on T2-weighted images and quantitative signal measurements on T2 mapping sequences. A total of 6 patients were treated with BM-MSCs and 5 patients received the sham procedure as part of control group. All patients reached 6 months follow up and a total of 8 patients reached 12 months follow up. VAS was significantly reduced after MSCs injection at 1, 3 and 6 months compared to the preoperative values (from 62.5 ± 13.3 preoperatively to 48.3 ± 11.7 at 1 month, 43.3 ± 12.1 at 3 months and 30 ± 22.8 at 6 months). ODI was significantly reduced at 3 and 6 months after MSCs injection compared to the baseline (from 26.33 ± 7.4 preoperatively to 15.67 ± 8.4 at 3 month and 12.00 ± 9.2 at 6 months). At 12 months, no statistical significance was shown in either groups. The SF-36 did not detect any significant change in terms of total score, physical or mental dimension score in both groups. WAI improved in the MSCs-treated group at 6 and 12 months compared to baseline (from score 20 ± 5,2 preoperatively to 31 ± 6,2 at 6 months and 39,6 ± 4 at 12 months). Water and proteoglycan content increased over time in patients treated with MSCs as shown by Pfirmann score (from preoperative grade 5 ± 0.15 to 4.25 ± 0.16 at 12 months) and T2 mapping ratio (0,6765 1/ms preoperatively to 0,784 1/ms at 6 months and 0,8605 1/ms at 12 months). In the present pilot study, the therapy with allogenic BM-MSCs has been proven to be an effective, safe and minimally invasive procedure. Indeed, patients treated with MSCs improved in terms of pain, disability, work ability and IVD water content measured by MRI. However, in order to assess the long-term benefits of this novel therapy, further clinical trials with larger patient populations and longer follow-up are mandatory.