Mesenchymal Stem Cells Use in the Treatment of Tendon Disorders: A Systematic Review and Meta-Analysis of Prospective Clinical Studies
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Objective To evaluate the efficacy and safety of mesenchymal stem cells (MSCs) therapy in patients with tendon disorders enrolled in prospective clinical studies. Methods We systematically searched prospective clinical studies that investigated the effects of MSC administration on human tendon disorders with at least a 6-month follow-up period in the PubMed-MEDLINE, EMBASE, and Cochrane Library databases. The primary outcome of interest was the change in pain on motion related to tendon disorders. Meta-regression analyses were performed to assess the relationship between MSC dose and pooled effect sizes in each cell dose. Results Four prospective clinical trials that investigated the effect of MSCs on tendon disorders were retrieved. MSCs showed a significant pooled effect size (overall Hedges’ g pooled standardized mean difference=1.868; 95% confidence interval, 1.274–2.462; p<0.001). The treatment with MSCs improved all the aspects analyzed, namely pain, functional scores, radiological parameters (magnetic resonance image or ultrasonography), and arthroscopic findings. In the meta-regression analysis, a significant cell dose-dependent response in pain relief (Q=9.06, p=0.029) was observed. Conclusion Our meta-analysis revealed that MSC therapy may improve pain, function, radiological, and arthroscopic parameters in patients with tendon disorders. A strong need for large-scale randomized controlled trials has emerged to confirm the long-term functional improvement and adverse effects of MSC therapies in tendon disorders.
Abstract
Objective To evaluate the efficacy and safety of mesenchymal stem cells (MSCs) therapy in patients with tendon disorders enrolled in prospective clinical studies. Methods We systematically searched prospective clinical studies that investigated the effects of MSC administration on human tendon disorders with at least a 6-month follow-up period in the PubMed-MEDLINE, EMBASE, and Cochrane Library databases. The primary outcome of interest was the change in pain on motion related to tendon disorders. Meta-regression analyses were performed to assess the relationship between MSC dose and pooled effect sizes in each cell dose. Results Four prospective clinical trials that investigated the effect of MSCs on tendon disorders were retrieved. MSCs showed a significant pooled effect size (overall Hedges’ g pooled standardized mean difference=1.868; 95% confidence interval, 1.274–2.462; p<0.001). The treatment with MSCs improved all the aspects analyzed, namely pain, functional scores, radiological parameters (magnetic resonance image or ultrasonography), and arthroscopic findings. In the meta-regression analysis, a significant cell dose-dependent response in pain relief (Q=9.06, p=0.029) was observed. Conclusion Our meta-analysis revealed that MSC therapy may improve pain, function, radiological, and arthroscopic parameters in patients with tendon disorders. A strong need for large-scale randomized controlled trials has emerged to confirm the long-term functional improvement and adverse effects of MSC therapies in tendon disorders.
참고문헌 (30)
- Young M, "Stem cell applications in tendon disorders : a clinical perspective", Stem Cells Int, 2012, pp.637836~ (2012)
- Barboni B, "Therapeutic potential of hAECs for early Achilles tendon defect repair through regeneration", J Tissue Eng Regen Med, 12, pp.e1594~ (2018)
- Liao GP, "Tissue engineering to repair diaphragmatic defect in a rat model", Stem Cells Int, 2017, pp.1764523~ (2017)
- Lee SY, "Therapeutic mechanisms of human adipose-derived mesenchymal stem cells in a rat tendon injury model", Am J Sports Med, 45, pp.1429~1439 (2017)
- Pas HI, "No evidence for the use of stem cell therapy for tendon disorders : a systematic review", Br J Sports Med, 51, pp.996~1002 (2017)
- Pascual-Garrido C, "Treatment of chronic patellar tendinopathy with autologous bone marrow stem cells : a 5-year-followup", Stem Cells Int, 2012, pp.953510~ (2012)
- Ellera Gomes JL, "Conventional rotator cuff repair complemented by the aid of mononuclear autologous stem cells", Knee Surg Sports Traumatol Arthrosc, 20, pp.373~377 (2012)
- Lee SY, "Treatment of lateral epicondylosis by using allogeneic adipose-derived mesenchymal stem cells : a pilot study", Stem Cells, 33, pp.2995~3005 (2015)
- Hernigou P, "Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears : a case-controlled study", Int Orthop, 38, pp.1811~1818 (2014)
- Havlas V, "Use of cultured human autologous bone marrow stem cells in repair of a rotator cuff tear : preliminary results of a safety study", Acta Chir Orthop Traumatol Cech, 82, pp.229~234 (2015)
- Lamas JR, "Adverse effects of xenogenic scaffolding in the context of a randomized double-blind placebo-controlled study for repairing full-thickness rotator cuff tears", Trials, 20, pp.387~ (2019)
- Wohn DY, "Korea okays stem cell therapies despite limited peer-reviewed data", Nat Med, 18, pp.329~ (2012)
- Shamseer L, "Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation", BMJ, 350, pp.g7647~ (2015)
- Tsikopoulos K, "The clinical impact of platelet-rich plasma on tendinopathy compared to placebo or dry needling injections : a meta-analysis", Phys Ther Sport, 17, pp.87~94 (2016)
- Ranger TA, "Is there an association between tendinopathy and diabetes mellitus? A systematic review with meta-analysis", Br J Sports Med, 50, pp.982~989 (2016)
- Begg CB, "Operating characteristics of a rank correlation test for publication bias", Biometrics, 50, pp.1088~1101 (1994)
- Egger M, "Bias in meta-analysis detected by a simple, graphical test", BMJ, 315, pp.629~634 (1997)
- Becker BJ, "Synthesizing standardized mean-change measures", Br J Math Stat Psychol, 41, pp.257~278 (1988)
- Jo CH, "Intratendinous injection of autologous adipose tissuederived mesenchymal stem cells for the treatment of rotator cuff disease : a first-in-human trial", Stem Cells, 36, pp.1441~1450 (2018)
- Andres BM, "Treatment of tendinopathy:what works, what does not, and what is on the horizon", Clin Orthop Relat Res, 466, pp.1539~1554 (2008)
- Mazzocca AD, "Rapid isolation of human stem cells(connective tissue progenitor cells)from the proximal humerus during arthroscopic rotator cuff surgery", Am J Sports Med, 38, pp.1438~1447 (2010)
- Nemoto M, "Tenascin-C expression in equine tendonderived cells during proliferation and migration", J Equine Sci, 24, pp.17~24 (2013)
- Kinnaird T, "Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms", Circulation, 109, pp.1543~1549 (2004)
- Seihee Yoon, "Efficacy and Safety of Intra-articular Injections of Hyaluronic Acid Combined With Polydeoxyribonucleotide in the Treatment of Knee Osteoarthritis", Annals of Rehabilitation Medicine, 43(2), pp.204~214 (2019), 대한재활의학회[DOI]
- Liang X, "Paracrine mechanisms of mesenchymal stem cell-based therapy : current status and perspectives", Cell Transplant, 23, pp.1045~1059 (2014)
- Squillaro T, "Clinical trials with mesenchymal stem cells : an update", Cell Transplant, 25, pp.829~848 (2016)
- Hare JM, "Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy : the POSEIDON randomized trial", JAMA, 308, pp.2369~2379 (2012)
- Machova Urdzikova L, "Human multipotent mesenchymal stem cells improve healing after collagenase tendon injury in the rat", Biomed Eng Online, 13, pp.42~ (2014)
- Coombes BK, "Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy : a systematic review of randomised controlled trials", Lancet, 376, pp.1751~1767 (2010)
- Carballo CB, "Cell-based approaches for augmentation of tendon repair", Tech Shoulder Elb Surg, 18, pp.e6~e14 (2017)