Meta-Analysis
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Meta-Anal. Jun 28, 2022; 10(3): 162-176
Published online Jun 28, 2022. doi: 10.13105/wjma.v10.i3.162
Is cellular therapy beneficial in management of rotator cuff tears? Meta-analysis of comparative clinical studies
Sathish Muthu, Cheruku Mogulesh, Vibhu Krishnan Viswanathan, Naveen Jeyaraman, Satvik N Pai, Madhan Jeyaraman, Manish Khanna
Sathish Muthu, Department of Orthopaedics, Government Medical College and Hospital, Dindigul 624001, Tamil Nadu, India
Sathish Muthu, Madhan Jeyaraman, Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201306, Uttar Pradesh, India
Sathish Muthu, Cheruku Mogulesh, Naveen Jeyaraman, Madhan Jeyaraman, Manish Khanna, Indian Stem Cell Study Group Association, Lucknow 226010, Uttar Pradesh, India
Cheruku Mogulesh, Naveen Jeyaraman, Department of Orthopaedic Rheuamtology, Dr Ram Manohar Lohiya National Law University, Lucknow 226010, Uttar Pradesh, India
Vibhu Krishnan Viswanathan, Department of MSK Oncology, University of Calgary, Alberta AB T2N 1N4, Alberta, Canada
Naveen Jeyaraman, Department of Orthopaedics, Atlas Hospitals (The Tamil Nadu Dr MGR Medical University), Tiruchirappalli 620002, Tamil Nadu, India
Satvik N Pai, Department of Orthopaedics, Sri Ramachandra Medical College and Research Institute, Chennai 600116, Tamil Nadu, India
Madhan Jeyaraman, Department of Orthopaedics, Faculty of Medicine, Sri Lalithambigai Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600095, Tamil Nadu, India
Madhan Jeyaraman, Manish Khanna, Department of Orthopaedics, South Texas Orthopaedic Research Institute (STORI Inc.), Laredo, TX 78045, United States
Manish Khanna, Department of Orthopaedics, Autonomous State Medical College, Ayodhya 224135, Uttar Pradesh, India
Author contributions: Muthu S conducted the research along with Viswanathan VK; Jeyaraman N, Patel K, Chellamuthu G, Jeyaraman M, and Khanna M helped in the conduction of the study; all authors have read and approved the final manuscript.
Conflict-of-interest statement: None of the authors have a conflict of interest over the subject presented.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Madhan Jeyaraman, MS, Assistant Professor, Department of Orthopaedics, Faculty of Medicine, Sri Lalithambigai Medical College and Hospital, Dr MGR Educational and Research Institute, Adayalampattu, Chennai 600095, Tamil Nadu, India. madhanjeyaraman@gmail.com
Received: February 4, 2022
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
Abstract
BACKGROUND

Mesenchymal stromal cell (MSC)-based cellular therapy promotes type I collagen production, enhance mechanical strength of tissues, and enhance biology at the bone-tendon interface, which primarily explains their potential clinical utility in rotator cuff (RC) tears.

AIM

To analyze the efficacy and safety of cellular therapy utilizing MSCs in the management of RC tears from clinical studies available in the literature.

METHODS

We conducted independent and duplicate electronic database searches including PubMed, Embase, Reference Citation Anallysis, Web of Science, and Cochrane Library in August 2021 for studies analyzing the efficacy and safety of cellular therapy (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.

RESULTS

Six studies involving 238 patients were included for analysis. We noted a significant reduction in VAS score for pain at 3 mo (weighed mean difference [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 significantly improved radiological tendon healing during the long-term follow-up (odds ratio [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-ups. We did not observe any significant increase in the adverse events directly related to cellular therapy, as compared with the control group (OR = 0.876, P = 0.869).

CONCLUSION

Based on our comprehensive and critical review, we could observe that the utilization of CT in RC tear significantly reduced pain severity at 3 and 6 mo, improved short-term functional outcome, enhanced radiological tendon healing, and mitigated retear rates at both short- and long-term follow-ups. The literature also confirmed the relative safety of using MSC therapy in patients presenting with RC tears.

Keywords: Mesenchymal stromal cell, Bone-marrow derived mesenchymal stromal cell, Adipose-derived mesenchymal stromal cell, Rotator cuff tear, Cellular therapy, Meta-analysis

Core Tip: Biological augmentation of rotator cuff tears with mesenchymal stromal cell-based cellular therapy significantly reduces the pain severity and improves the functional outcome at 3 and 6 mo based on our critical review of clinical studies on the subject. Moreover, we noted enhanced radiological tendon healing, and mitigated retear rates at both short- and long-term follow-ups. We have also established the safety of using cellular therapy in patients presenting with rotator cuff tears.