Informed consent was obtained from patients who had a relevant history and compatible findings in physical/ultrasonographic examinations. The screening included taking the history of shoulder pain, examining the range of motion of the shoulder, performing empty can tests, and evaluating ultrasonographic findings. Volunteers were screened by a physiatrist subspecializing in musculoskeletal rehabilitation (L.CY, C.SW) with at least 5 years of clinical practice and experience in ultrasonographic examination. Participants Screening, enrollment, and random allocation
#Stem cell treatment for shoulders trial
The trial was conducted according to the principles in the Declaration of Helsinki and followed the Good Clinical Practice guidelines.
Written informed consent was obtained from all participants prior to the enroll. The trial ended as scheduled after recruiting the target population. The protocol ( Identifier: NCT02298023, first registration: ) and informed consent were approved prior to the trial. We adopted a three-arm study design including intervention, active control, and control groups. This randomized placebo-controlled trial was conducted from November 2014 to April 2018 at Seoul National University Hospital in Seoul, Korea. We hypothesized that delivering MSCs into tear lesions, partial tears of the supraspinatus tendon in this study, would augment the extent and rate of clinical improvement compared with delivering control injectates and that the MSC injection would be well tolerated. Therefore, in this study, we conducted the first randomized, placebo-controlled trial to investigate the effects of MSC injection into tendinous lesions. A comparative clinical trial is warranted to verify the clinical efficacy of MSCs in rotator cuff tears. However, the single-arm study design could not exclude the effects of natural recovery, adjunctive treatments, and the placebo effect, preventing them from making conclusions regarding the real effects of MSC injection. The authors even observed complete resolution of the tendon tear in some participants via arthroscopy. Recently, a clinical trial on intra-tendon MSC injection for rotator cuff tear reported promising results 8. Thus, replenishing the local cell population with stem cells to augment the regenerative potential of the tendon is appealing as a novel treatment for tendinopathy.Īmid positive reports from stem cell clinical trials for connective tissue lesions, i.e., Crohn’s anal fistula 4 and bony fracture 5, the efficacy of mesenchymal stem cell (MSC)-mediated tendon regeneration has been demonstrated by its structural and biomechanical effects in various animal models of tendinopathy 6, 7. However, the mature tendon is sparsely populated by cells, accounting for approximately 5% of the tissue volume, of which less than 1% possess progenitor cell properties 3. Even mechanical loading within the physiological capacity of the tendon can damage the microstructure when applied repetitively 1 this damage can be repaired by intrinsic healing processes orchestrated by tenoblasts 2. The function of the tendon to transmit force generated by the muscle to the bone results in perpetual tension with or without compression and friction. Stem cell injection into supraspinatus partial tears in patients with shoulder pain lasting more than 3 months was not more effective than control injections.Ĭ Identifier: NCT02298023 Safety measures did not differ between groups, and there were no persistent adverse events. There were no differences in post-injection pain duration or severity. All participants reported transient pain at the injection site. Only time significantly predicted the outcome measure. A mixed effect model revealed no statistically significant interactions. Primary outcome did not differ among groups ( p = 0.35). Twenty-three patients were included in the final analysis.
The primary outcome measure was the improvement in pain at activity at 3 months after injection.
Participants were followed up at 6, 12 weeks, 6, 12 months and 2 years after injection. For safety measures, laboratory tests were taken and adverse events were recorded at every visit. Pain at activity and rest, shoulder function and tear size were evaluated. Participants were assigned to three groups: stem cells in fibrin glue, normal saline/fibrin glue mixture, and normal saline only, with which intra-lesional injection was performed. We enrolled 24 patients with shoulder pain lasting more than 3 months and partial tears in the supraspinatus tendon. We performed a randomized, controlled study to investigate the effects of mesenchymal stem cell injection for treating partial tears in the supraspinatus tendon. Thus, the injured tendon might be treated successfully by stem cell transplantation. Tendons have limited reparative ability and perform a relatively simple mechanical function via the extracellular matrix.