Objectives To assess the efficacy of a single intradiscal injection of allogeneic bone marrow mesenchymal stromal cells (BM-MSCs) versus a sham placebo in patients with chronic low back pain (LBP). Methods Participants were randomised in a prospective, double-blind, controlled study to receive either sham injection or intradiscal injection of 20 million allogeneic BM-MSC, between April 2018 and December 2022. The first co-primary endpoint was the rate of responders defined by improvement of the Visual Analogue Scale (VAS) for pain of at least 20% and 20 mm, or improvement of the Oswestry Disability Index (ODI) of 20% between baseline and month 12. The secondary structural co-primary endpoint was assessed by the disc fluid content measured by quantitative MRI T2, between baseline and month 12. Secondary endpoints included pain VAS, ODI, the Short Form (SF)-36 and the minimal clinically important difference in all timepoints (1, 3, 6, 12 and 24 months). We determined the immune response associated with allogeneic cell injection between baseline and 6 months. Serious adverse events (SAEs) were recorded. Results 114 patients were randomised (n=58, BM-MSC group; n=56, sham placebo group). At 12 months, the primary outcome was not reached (74% in the BM-MSC group vs 69% in the placebo group; p=0.77). The groups did not differ in all secondary outcomes. No SAE related to the intervention occurred. Conclusions While our study did not conclusively demonstrate the efficacy of allogeneic BM-MSCs for LBP, the procedure was safe. Long-term outcomes of MSC therapy for LBP are still being studied. Trial registration number EudraCT 2017-002092-25/ClinicalTrials.gov: NCT03737461.

Introduction: Patellar tendon overuse injuries are common in athletes. Imaging may show a change in tissue structure with tendon thickening and disruption of the intratendinous substance. We wish to test the hypothesis that both autologous bone marrow expanded mesenchymal stem cells and autologous leukocyte-poor platelet-rich plasma (LP-PRP) implanted into the area of the disrupted tendinopathic patellar tendon will restore function, but tendon regeneration tissue will only be observed in the subjects treated with autologous bone marrow expanded mesenchymal stem cells. Methods and analysis: This is a single-centre, pilot phase I/II, double-blinded clinical trial with randomisation with active control. Twenty patients with a diagnosis of patellar tendinopathy with imaging changes (tendon thickening and disruption of the intratendinous substance at the proximal portion of the patellar tendon) will be randomised in a 1:1 ratio to receive a local injection of either bone-marrow autologous mesenchymal stem cells (MSC), isolated and cultured under GMP at The Institute of Biology and Molecular Genetics (IBGM) (Spain) or P-PRP. The study will have two aims: first, to ascertain whether a clinically relevant improvement after 3, 6 and 12 months according to the visual analogue scale (VAS), Victorian Institute of Sport Assessment for patellar tendons (VISA-P) and dynamometry scales (DYN) will be achieved; and second, to ascertain whether the proposed intervention will restore tendon structure as determined by ultrasonography (US), Doppler ultrasonography (DUS), and innovative MRI and ultrasound techniques: Magnetic Resonance T2 FAT SAT (UTE, Ultrashort Echo TE) sequence and Ultrasound Tissue Characterization (UTC). Patients who are randomised to the P-PRP treatment group but do not achieve a satisfactory primary endpoint after 6 months will be offered treatment with MSC. Trial registration: NCT03454737.

Background: In a previous study, the authors found that at 6 months after treatment with a 20 × 10⁶ dose of bone marrow–derived mesenchymal stem cells (BM-MSCs), patients showed improved tendon structure and regeneration of the gap area when compared with treatment using leukocyte-poor platelet-rich plasma (Lp-PRP). The Lp-PRP group (n = 10), which had not seen tendon regeneration at the 6-month follow-up, was subsequently offered treatment with BM-MSCs to see if structural changes would occur. In addition, the 12-month follow-up outcomes of the original BM-MSC group (n = 10) were evaluated. Purpose: To evaluate the outcomes of all patients (n = 20) at 12 months after BM-MSC treatment and observe if the Lp-PRP pretreated group experienced any type of advantage. Study Design: Cohort study; Level of evidence, 2. Methods: Both the BM-MSC and original Lp-PRP groups were assessed at 12 months after BM-MSC treatment with clinical examination, the visual analog scale (VAS) for pain during daily activities and sports activities, the Victorian Institute of Sport Assessment–Patella score for patellar tendinopathy, dynamometry, and magnetic resonance imaging (MRI). Differences between the 2 groups were compared with the Student t test. Results: The 10 patients originally treated with BM-MSCs continued to show improvement in tendon structure in their MRI scans ( P < .0001), as well as in the clinical assessment of their pain by means of scales ( P < .05). Ten patients who were originally treated with Lp-PRP and then with BM-MSCs exhibited an improvement in tendon structure in their MRI scans, as well as a clinical pain improvement, but this was not significant on the VAS for sports ( P = .139). Thus, applying Lp-PRP before BM-MScs did not yield any type of advantage. Conclusion: The 12-month follow-up outcomes after both groups of patients (n = 20) received BM-MSC treatment indicated that biological treatment was safe, there were no adverse effects, and the participants showed a highly statistically significant clinical improvement ( P < .0002), as well as an improvement in tendon structure on MRI ( P < .0001). Preinjection of Lp-PRP yielded no advantages.

Objective quantification of tendon structural changes through imaging is only achieved by evaluating tendon structure using ultrasound tissue characterization (UTC) technology. This study compares the effects of bone marrow mesenchymal stromal cells (BM-MSC) and leukocyte-poor platelet-rich plasma (Lp-PRP) on tendon structure and clinical outcomes in male patients with patellar tendinopathy measured with UTC at 3, 6, and 12 months after treatment. This is a double-blinded clinical trial with a randomized active control study with 20 male patients diagnosed with patellar tendinopathy who underwent BM-MSC and Lp-PRP. Bilateral ultrasound tissue characterization scans of the patellar tendon were carried out after 3, 6, and 12 months, as well as tests for strength and pain. UTC patellar tendon was analyzed at the insertion, proximal, and mid-tendon. BM-MSC showed a greater capacity to promote further positive changes than Lp-PRP. Lp-PRP presented higher disorganized echo-type II in the mid-tendon (p = 0.04; ES = 1.06) and III (p = 0.02; ES = −1.47) after 3 months in the Lp-PRP group. Similar results were seen after 6 and 12 months. Pain and strength data show improvement in the treated tendon. BM-MSC treatment demonstrates a superior capacity to promote tendon regeneration and organization, restore strength, and reduce pain compared to Lp-PRP, after 3, 6, and 12 months in male patients with patellar tendinopathy.