Published online Jun 28, 2022. doi: 10.13105/wjma.v10.i3.162
Peer-review started: February 4, 2022
First decision: April 19, 2022
Revised: May 2, 2022
Accepted: June 22, 2022
Article in press: June 22, 2022
Published online: June 28, 2022
Processing time: 151 Days and 1 Hours
Rotator cuff (RC) tear is a common shoulder pathology, whose prevalence ranges from 4% in asymptomatic individuals younger than 40 years to 54% in patients aged over 60 years. The etiology of these tears is multifactorial, and has been variously attributed to traumatic, mechanical, and inflammatory processes. It has been well-demonstrated that the natural course of non-operatively managed RC tears in the majority of patients is a progressive deterioration of the anatomical tear without spontaneous regression of symptoms. On the other hand, although surgical repair of a torn RC potentially aids in restoring the shoulder function as well as arresting the tear progression, the failure rates range between 0 and 78%, thereby giving room for improvement.
Recently, mesenchymal stromal cells (MSCs) have been successfully employed in diverse animal and human models in the repair of various musculoskeletal structures like cartilages, bones, muscles, and tendons. These cells (usually extracted from bone marrow or adipose tissue) possess a unique attribute described as “multipotency”, which denotes their ability to differentiate into other tissues of mesenchymal origin. When delivered using appropriate scaffolds, these modalities of cellular therapy (CT) have shown great promise in enhancing the outcome following RC tears, too. MSCs are thought to promote type I collagen production, enhance mechanical strength of tissues, and ameliorate biology at the bone-tendon interface, which primarily explains their potential clinical utility in RC tears. The concentrates of these cells may be delivered into the region of tendon injury, either via image-guided injections or through arthroscopic approach (intra-operatively). However, the major barriers to regular use of MSCs include lack of standardized techniques for preparation, inadequate clinical evidence, and potentially high cost:benefit ratios.
To analyze the efficacy and safety of CT utilizing MSCs in the management of RC tears from clinical studies available in the literature.
We conducted independent and duplicate electronic database searches including PubMed, Embase, Web of Science, and Cochrane Library on August 2021 for studies analyzing the efficacy and safety of CT utilizing MSCs in the management of RC tears. Visual Analog Score (VAS) score for pain, American Shoulder and Elbow Surgeons (ASES) score, Disability of the Arm, Shoulder and Hand score, Constant score, radiological assessment of healing, and complications such as retear rate and adverse events were the outcomes analyzed. Analysis was performed in R-platform using OpenMeta [Analyst] software.
Six studies involving 238 patients were included for analysis. We noted a significant reduction in VAS score for pain at 3 mo (WMD = -2.234, P < 0.001) and 6 mo (WMD = -3.078, P < 0.001) with the use of CT, which was not maintained at long-term follow-up (WMD = -0.749, P = 0.544). Concerning functional outcomes, utilization of CT produced a significant short-term improvement in the ASES score (WMD = 17.090, P < 0.001) and significant benefit in functional scores such as Constant score (WMD = 0.833, P = 0.760) at long-term follow-up. Moreover, we also observed a significantly improved radiological tendon healing during the long-term follow-up (OR = 3.252, P = 0.059). We also noted a significant reduction in the retear rate upon utilization of CT in RC tears both at short- (OR = 0.079, P = 0.032) and long-term (OR = 0.434, P = 0.027) follow-up. We did not observe any significant increase in the adverse events directly related to CT, as compared with the control group (OR = 0.876, P = 0.869).
Based on our comprehensive and critical review of the available literature analyzing the efficacy and safety of CT utilizing MSCs in the management of RC tears, we could observe that the utilization of CT significantly reduced pain severity at 3 and 6 mo, improved short-term functional outcome, enhanced radiological tendon healing, and mitigated retear rates at short- and long-term follow-up. The literature did not reveal any major adverse events directly related to MSC therapy in patients presenting with RC tears.
We recommend a large-scale, multicentric trial analyzing autologous and allogeneic sources of MSCs with standardized dosage and intervention protocol, evaluated with established outcome measures both at short- and long-term follow-up to further confirm the results of our analysis.