Adverse effects of xenogenic scaffolding in the context of a randomized double-blind placebo-controlled study for repairing full-thickness rotator cuff tears

Abstract

Purpose The purpose of the study was to compare the safety and efficacy of autologous mesenchymal stem cells (MSCs) embedded in a xenogenic scaffold for repairing the supraspinatus tendon. Methods This was a randomized, double-blind and placebo-controlled trial evaluating patients with full-thickness rotator cuff tears (Eudra-CT, 2007–007630-19). Effectiveness was evaluated using the Constant score and a visual analogue pain scale (VAS). Constant score has four domains including pain (15 possible points), activities of daily living (20 possible points), mobility (40 possible points), and strength (25 possible points). Scores range from 0 points (most disability) to 100 points (least disability). The structural integrity of the repaired tendon was assessed by magnetic resonance imaging (MRI) according to Patte and Thomazeau classification criteria. The primary study end point was an improvement in the Constant score by 20 points at one year compared to initial assessment. Results The trial was stopped due to adverse effects observed in both groups. Only thirteen patients were included and analyzed. The Constant questionnaire showed a significant improvement in the MSC treatment group compared with the preoperative data (p = 0.0073). Secondary outcome measures were similar in both groups. Conclusions Our study showed preliminary inconclusive clinical outcomes in the patients treated with MSCs. Adverse events revealed the need for further approaches using scaffolds of a different nature or perhaps no scaffolds, in the context of small joints. Trial registration Eudra-CT, 2007-007630-19 . Registered on 30 January 2008. Level of evidence A Level 1 of evidence treatment study. Electronic supplementary material The online version of this article (10.1186/s13063-019-3504-3) contains supplementary material, which is available to authorized users.

Current Evidence of Mesenchymal Stem Cells Use in the Treatment of Tendon Disorders: A Systematic Review, Meta-analysis, and Meta-regression of Prospective Clinical Studies

“…After duplicates were removed, the titles and abstracts of 897 articles were initially screened and 25 selected for full-text review. The full-text articles were read and 4 were considered relevant by qualitative analysis [8,10,11,19]. The studies selected for final inclusion or exclusion are shown in Figure 1, and the characteristics of the included studies are summarized in Table 1.…”

“…In terms of quantitative analysis, these four studies (published from 2015 to 2019) fulfilled our inclusion criteria. Three papers [8,10,19] were open-label prospective studies, while one [11] was a double-blind randomized controlled trial. The studies identified for meta-analysis included 52 participants.…”

“…The studies identified for meta-analysis included 52 participants. Two studies [8,19] employed adipose tissuederived MSCs and the other two [10,11] administered bone marrow-derived MSCs. The number of cells used in each study ranges from 10 6 to a maximum of 10 8 .…”

“…In the studies included in this meta-analysis, most of the reported adverse events were not related to treatment ( Table 2). The treatment-related side effects were mild joint effusion and regional swelling following allogeneic stem cell injection [8] or engrafted patchrelated foreign body reaction [11]. The joint swelling spontaneously subsided, while the patch-related adverse event needed additional surgery.…”

“…Moreover, this study was not carried out with the meta-analysis methodology, which combines the results from multiple studies. Furthermore, two current clinical studies [10,11], which used isolated MSCs on tendon disorder, were not included in the review.…”