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
Abstract
BACKGROUND

Osteoarthritis (OA) is the most common joint disorder, is associated with an increasing socioeconomic impact owing to the ageing population.

AIM

To analyze and compare the efficacy and safety of bone-marrow-derived mesenchymal stromal cells (BM-MSCs) and adipose tissue-derived MSCs (AD-MSCs) in knee OA management from published randomized controlled trials (RCTs).

METHODS

Independent and duplicate electronic database searches were performed, including PubMed, EMBASE, Web of Science, and Cochrane Library, until August 2021 for RCTs that analyzed the efficacy and safety of AD-MSCs and BM-MSCs in the management of knee OA. 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 score, knee osteoarthritis outcome score (KOOS), and adverse events were analyzed. Analysis was performed on the R-platform using OpenMeta (Analyst) software. Twenty-one studies, involving 936 patients, were 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.

RESULTS

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).

CONCLUSION

Adipose tissue is superior to bone marrow because of its safety and consistent efficacy in improving pain and functional outcomes. Future trials are urgently warranted to validate our findings and reach a consensus on the ideal source of MSCs for managing knee OA.

Keywords: Mesenchymal stromal cell, Adipose tissue-derived mesenchymal stromal cell, Bone-marrow derived mesenchymal stromal cell, Cartilage regeneration, Knee osteoarthritis, Meta-analysis, Efficacy, Safety

Core Tip: With the ongoing rise in the exploration of the clinical efficacy of mesenchymal stromal cells (MSCs) in the management of osteoarthritis (OA), there is an imminent need to identify the ideal source of MSCs to be utilized. Our meta-analysis has brought out the lacunae in the literature for studies to evaluate the impact of the source of MSCs in the management of OA. From a single-arm meta-analysis of available studies on the two commonly used sources such as bone marrow (BM) and adipose tissue, we found the adipose tissue to be superior to BM concerning the safety and consistent efficacy in improving pain and functional outcomes. However, considering the paucity of evidence, we recommend future trials to validate our findings and reach a consensus on the ideal source of MSCs for managing knee OA.