Meta-Analysis
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Orthop. Jan 18, 2023; 14(1): 23-41
Published online Jan 18, 2023. doi: 10.5312/wjo.v14.i1.23
Comparative effectiveness of adipose-derived mesenchymal stromal cells in the management of knee osteoarthritis: A meta-analysis
Sathish Muthu, Sandesh C Patil, Naveen Jeyaraman, Madhan Jeyaraman, Prakash Gangadaran, Ramya Lakshmi Rajendran, Eun Jung Oh, Manish Khanna, Ho Yun Chung, Byeong-Cheol Ahn
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 201310, Uttar Pradesh, India
Sathish Muthu, Madhan Jeyaraman, Research Associate, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
Sathish Muthu, Naveen Jeyaraman, Madhan Jeyaraman, Manish Khanna, Indian Stem Cell Study Group Association, Lucknow 226001, Uttar Pradesh, India
Sandesh C Patil, Naveen Jeyaraman, Department of Orthopaedic Rheumatology, Dr. RML National Law University, Lucknow 226012, Uttar Pradesh, India
Madhan Jeyaraman, Department of Orthopaedics, ACS Medical College & Hospital, Dr MGR Educational and Research Institute, Chennai 600056, Tamil Nadu, India
Prakash Gangadaran, Ho Yun Chung, Byeong-Cheol Ahn, BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
Prakash Gangadaran, Ramya Lakshmi Rajendran, Byeong-Cheol Ahn, Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
Eun Jung Oh, Ho Yun Chung, Department of Plastic and Reconstructive Surgery, CMRI, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, South Korea
Ho Yun Chung, Department of Plastic and Reconstructive Surgery, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
Byeong-Cheol Ahn, Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu 41944, South Korea
Author contributions: Muthu S, Patil SC, Jeyaraman N, and Jeyaraman M involved in the conception and design of the manuscript; Gangadaran P, Rajendran RL, Oh EJ, Khanna M, Chung HY, and Ahn BC contributed to the administrative support; Muthu S, Patil SC, Jeyaraman N, Jeyaraman M, and Khanna M participated in the provision of study materials or patients; Muthu S, Patil SC and Jeyaraman N involved in the collection and assembly of data; Muthu S, Patil SC, Jeyaraman N, Jeyaraman M, Gangadaran P, Chung HY, and Ahn BC analysied and interpreted data; Muthu S, Patil SC, Jeyaraman N, Jeyaraman M, Gangadaran P, Rajendran RL, Oh EJ, Khanna M, Chung HY, and Ahn BC wrote the manuscript writing; Muthu S, Chung HY and Ahn BC are co-corresponding authors of this manuscript; Gangadaran P, Rajendran RL and Chung HY contributed to the funding acquisition; and all authors have read and agreed to the published version of the manuscript.
Supported by the Basic Science Research Program through the National Research Foundation of Korea, NRF-2021R1I1A1A01040732 and NRF-2022R1I1A1A01068652; and the National Research Foundation of Korea grant funded by the Korean Government, Ministry of Science and ICT, 2020R1A2C2009496.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Byeong-Cheol Ahn, MD, PhD, Professor, Department of Nuclear Medicine, School of Medicine, Kyungpook National University, 680 Gukchaebosangro, Junggu, Daegu 41944, South Korea. abc2000@knu.ac.kr
Received: September 14, 2022
Peer-review started: September 14, 2022
First decision: October 17, 2022
Revised: October 20, 2022
Accepted: December 13, 2022
Article in press: December 13, 2022
Published online: January 18, 2023
Processing time: 121 Days and 2.4 Hours
ARTICLE HIGHLIGHTS
Research background

Mesenchymal stromal cell (MSC)-based therapies are being commonly utilized in the context of knee osteoarthritis (OA) with promising results. The commonly used sources of the MSC remain in the bone marrow (BM) and the adipose derived (AD).

Research motivation

Despite the prevalence of the use of MSCs of varying origins in the management of knee OA, the literature is not clear on the ideal source to focus on for future research.

Research objectives

In this study, we aim to compare the efficacy and safety of the two commonly used sources of MSCs namely BM and adipose tissue in the management of knee OA.

Research methods

We conducted a systematic review and meta-analysis of the randomized controlled trials (RCTs) in the literature identified from databases such as PubMed, EMBASE, Web of Science, and Cochrane Library until August 2021 that analyzed the efficacy and safety of AD and BM-MSCs in the management of knee OA. we used outcome parameters such as the visual analog scale (VAS) score for pain, Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), Lysholm score, Tegner score, magnetic resonance observation of cartilage repair tissue (MOCART) score, knee osteoarthritis outcome score (KOOS), and adverse events.

Research results

We identified twenty-one studies including 936 patients. Of all the studies included, only one study compared the two MSC sources without patient randomization; hence, the results of all included studies from both sources were pooled, and a comparative critical analysis was performed. At six months, both AD-MSCs and BM-MSCs showed significant VAS improvement (P = 0.015, P = 0.012); this was inconsistent at 1 year for BM-MSCs (P < 0.001, P = 0.539), and AD-MSCs outperformed BM-MSCs compared to controls in measures such as WOMAC (P < 0.001, P = 0.541), Lysholm scores (P = 0.006; P = 0.933), and KOOS (P = 0.002; P = 0.012). BM-MSC-related procedures caused significant adverse events (P = 0.003) compared to AD-MSCs (P = 0.673).

Research conclusions

Our study identified adipose tissue to be superior to BM in terms of its safety and consistent efficacy in improving the pain and functional outcome parameters analyzed.

Research perspectives

We suggest for future RCTs be conducted to make a direct comparison of the two sources considering the paucity of the literature identified in this study and also to validate the findings arrived in the study.