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Research ArticleArticle

Effect of Stem Cell Injections on Osteoarthritis-related Structural Outcomes: A Systematic Review

Jennifer Gong, Jessica Fairley, Flavia M. Cicuttini, Sultana Monira Hussain, Rakhi Vashishtha, Louisa Chou, Anita E. Wluka and Yuanyuan Wang
The Journal of Rheumatology October 2020, jrheum.200021; DOI: https://doi.org/10.3899/jrheum.200021
Jennifer Gong
SMH is the recipient of National Health and Medical Research Council (NHMRC) Early Career Fellowship (APP1142198). LC is the recipient of an Australian Postgraduate Award and Arthritis Foundation Scholarship. AEW and YW are the recipients of NHMRC Translating Research into Practice Fellowship (APP1150102 and APP1168185, respectively). J. Gong, BBiomedSc (Hons), J. Fairley, MBBS, F.M. Cicuttini, MBBS, FRACP, PhD, S.M. Hussain, MBBS, MPH, PhD, L. Chou, MBBS, FRACP, A.E. Wluka, MBBS, FRACP, PhD, Y. Wang, MBBS, MMed, PhD, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University; R. Vashishtha, BDS, MPH, Center for Alcohol Policy Research, School of Psychology and Public Health, La Trobe University, Melbourne, Australia. The authors have no conflicts of interest. Address correspondence to Dr. Y. Wang, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC 3004, Australia. Email: yuanyuan.wang@monash.edu. Accepted for publication September 24, 2020.
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Jessica Fairley
SMH is the recipient of National Health and Medical Research Council (NHMRC) Early Career Fellowship (APP1142198). LC is the recipient of an Australian Postgraduate Award and Arthritis Foundation Scholarship. AEW and YW are the recipients of NHMRC Translating Research into Practice Fellowship (APP1150102 and APP1168185, respectively). J. Gong, BBiomedSc (Hons), J. Fairley, MBBS, F.M. Cicuttini, MBBS, FRACP, PhD, S.M. Hussain, MBBS, MPH, PhD, L. Chou, MBBS, FRACP, A.E. Wluka, MBBS, FRACP, PhD, Y. Wang, MBBS, MMed, PhD, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University; R. Vashishtha, BDS, MPH, Center for Alcohol Policy Research, School of Psychology and Public Health, La Trobe University, Melbourne, Australia. The authors have no conflicts of interest. Address correspondence to Dr. Y. Wang, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC 3004, Australia. Email: yuanyuan.wang@monash.edu. Accepted for publication September 24, 2020.
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Flavia M. Cicuttini
SMH is the recipient of National Health and Medical Research Council (NHMRC) Early Career Fellowship (APP1142198). LC is the recipient of an Australian Postgraduate Award and Arthritis Foundation Scholarship. AEW and YW are the recipients of NHMRC Translating Research into Practice Fellowship (APP1150102 and APP1168185, respectively). J. Gong, BBiomedSc (Hons), J. Fairley, MBBS, F.M. Cicuttini, MBBS, FRACP, PhD, S.M. Hussain, MBBS, MPH, PhD, L. Chou, MBBS, FRACP, A.E. Wluka, MBBS, FRACP, PhD, Y. Wang, MBBS, MMed, PhD, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University; R. Vashishtha, BDS, MPH, Center for Alcohol Policy Research, School of Psychology and Public Health, La Trobe University, Melbourne, Australia. The authors have no conflicts of interest. Address correspondence to Dr. Y. Wang, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC 3004, Australia. Email: yuanyuan.wang@monash.edu. Accepted for publication September 24, 2020.
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Sultana Monira Hussain
SMH is the recipient of National Health and Medical Research Council (NHMRC) Early Career Fellowship (APP1142198). LC is the recipient of an Australian Postgraduate Award and Arthritis Foundation Scholarship. AEW and YW are the recipients of NHMRC Translating Research into Practice Fellowship (APP1150102 and APP1168185, respectively). J. Gong, BBiomedSc (Hons), J. Fairley, MBBS, F.M. Cicuttini, MBBS, FRACP, PhD, S.M. Hussain, MBBS, MPH, PhD, L. Chou, MBBS, FRACP, A.E. Wluka, MBBS, FRACP, PhD, Y. Wang, MBBS, MMed, PhD, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University; R. Vashishtha, BDS, MPH, Center for Alcohol Policy Research, School of Psychology and Public Health, La Trobe University, Melbourne, Australia. The authors have no conflicts of interest. Address correspondence to Dr. Y. Wang, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC 3004, Australia. Email: yuanyuan.wang@monash.edu. Accepted for publication September 24, 2020.
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Rakhi Vashishtha
SMH is the recipient of National Health and Medical Research Council (NHMRC) Early Career Fellowship (APP1142198). LC is the recipient of an Australian Postgraduate Award and Arthritis Foundation Scholarship. AEW and YW are the recipients of NHMRC Translating Research into Practice Fellowship (APP1150102 and APP1168185, respectively). J. Gong, BBiomedSc (Hons), J. Fairley, MBBS, F.M. Cicuttini, MBBS, FRACP, PhD, S.M. Hussain, MBBS, MPH, PhD, L. Chou, MBBS, FRACP, A.E. Wluka, MBBS, FRACP, PhD, Y. Wang, MBBS, MMed, PhD, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University; R. Vashishtha, BDS, MPH, Center for Alcohol Policy Research, School of Psychology and Public Health, La Trobe University, Melbourne, Australia. The authors have no conflicts of interest. Address correspondence to Dr. Y. Wang, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC 3004, Australia. Email: yuanyuan.wang@monash.edu. Accepted for publication September 24, 2020.
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Louisa Chou
SMH is the recipient of National Health and Medical Research Council (NHMRC) Early Career Fellowship (APP1142198). LC is the recipient of an Australian Postgraduate Award and Arthritis Foundation Scholarship. AEW and YW are the recipients of NHMRC Translating Research into Practice Fellowship (APP1150102 and APP1168185, respectively). J. Gong, BBiomedSc (Hons), J. Fairley, MBBS, F.M. Cicuttini, MBBS, FRACP, PhD, S.M. Hussain, MBBS, MPH, PhD, L. Chou, MBBS, FRACP, A.E. Wluka, MBBS, FRACP, PhD, Y. Wang, MBBS, MMed, PhD, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University; R. Vashishtha, BDS, MPH, Center for Alcohol Policy Research, School of Psychology and Public Health, La Trobe University, Melbourne, Australia. The authors have no conflicts of interest. Address correspondence to Dr. Y. Wang, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC 3004, Australia. Email: yuanyuan.wang@monash.edu. Accepted for publication September 24, 2020.
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Anita E. Wluka
SMH is the recipient of National Health and Medical Research Council (NHMRC) Early Career Fellowship (APP1142198). LC is the recipient of an Australian Postgraduate Award and Arthritis Foundation Scholarship. AEW and YW are the recipients of NHMRC Translating Research into Practice Fellowship (APP1150102 and APP1168185, respectively). J. Gong, BBiomedSc (Hons), J. Fairley, MBBS, F.M. Cicuttini, MBBS, FRACP, PhD, S.M. Hussain, MBBS, MPH, PhD, L. Chou, MBBS, FRACP, A.E. Wluka, MBBS, FRACP, PhD, Y. Wang, MBBS, MMed, PhD, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University; R. Vashishtha, BDS, MPH, Center for Alcohol Policy Research, School of Psychology and Public Health, La Trobe University, Melbourne, Australia. The authors have no conflicts of interest. Address correspondence to Dr. Y. Wang, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC 3004, Australia. Email: yuanyuan.wang@monash.edu. Accepted for publication September 24, 2020.
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Yuanyuan Wang
SMH is the recipient of National Health and Medical Research Council (NHMRC) Early Career Fellowship (APP1142198). LC is the recipient of an Australian Postgraduate Award and Arthritis Foundation Scholarship. AEW and YW are the recipients of NHMRC Translating Research into Practice Fellowship (APP1150102 and APP1168185, respectively). J. Gong, BBiomedSc (Hons), J. Fairley, MBBS, F.M. Cicuttini, MBBS, FRACP, PhD, S.M. Hussain, MBBS, MPH, PhD, L. Chou, MBBS, FRACP, A.E. Wluka, MBBS, FRACP, PhD, Y. Wang, MBBS, MMed, PhD, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University; R. Vashishtha, BDS, MPH, Center for Alcohol Policy Research, School of Psychology and Public Health, La Trobe University, Melbourne, Australia. The authors have no conflicts of interest. Address correspondence to Dr. Y. Wang, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC 3004, Australia. Email: yuanyuan.wang@monash.edu. Accepted for publication September 24, 2020.
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Abstract

Objective To systematically review the evidence for the efficacy of mesenchymal stem cell (MSC) injections in improving osteoarthritis (OA)-related structural outcomes.

Methods Ovid Medline and EMBASE were searched from their inceptions to April 2020 using MeSH terms and key words. Independent reviewers extracted data and assessed methodological quality. Qualitative evidence synthesis was performed due to the heterogeneity of interventions and outcome measures.

Results Thirteen randomized controlled trials (phase I or II) were identified: 10 in OA populations and 3 in populations at risk of OA, with low (n = 9), moderate (n = 3), or high (n = 1) risk of bias. Seven studies used allogeneic MSCs (4 bone marrow, 1 umbilical cord, 1 placenta, 1 adipose tissue), 6 studies used autologous MSCs (3 adipose tissue, 2 bone marrow, 1 peripheral blood). Among the 11 studies examining cartilage outcomes, 10 found a benefit of MSCs on cartilage volume, morphology, quality, regeneration, and repair, assessed by magnetic resonance imaging, arthroscopy, or histology. The evidence for subchondral bone was consistent in all 3 studies in populations at risk of OA, showing beneficial effects. Sixteen unpublished, eligible trials were identified by searching trial registries, including 8 with actual or estimated completion dates before 2016.

Conclusion Our systematic review of early-phase clinical trials demonstrated consistent evidence of a beneficial effect of intraarticular MSC injections on articular cartilage and subchondral bone. Due to the heterogeneity of MSCs, modest sample sizes, methodological limitations, and potential for publication bias, further work is needed before this therapy is recommended in the management of OA.

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Effect of Stem Cell Injections on Osteoarthritis-related Structural Outcomes: A Systematic Review
Jennifer Gong, Jessica Fairley, Flavia M. Cicuttini, Sultana Monira Hussain, Rakhi Vashishtha, Louisa Chou, Anita E. Wluka, Yuanyuan Wang
The Journal of Rheumatology Oct 2020, jrheum.200021; DOI: 10.3899/jrheum.200021

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Effect of Stem Cell Injections on Osteoarthritis-related Structural Outcomes: A Systematic Review
Jennifer Gong, Jessica Fairley, Flavia M. Cicuttini, Sultana Monira Hussain, Rakhi Vashishtha, Louisa Chou, Anita E. Wluka, Yuanyuan Wang
The Journal of Rheumatology Oct 2020, jrheum.200021; DOI: 10.3899/jrheum.200021
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