Mesenchymal Stem Cells Use in the Treatment of Tendon Disorders: A Systematic Review and Meta-Analysis of Prospective Clinical Studies

Overview

Journal Ann Rehabil Med

Specialty Rehabilitation Medicine

Date 2021 Sep 9

PMID 34496470

Citations 9

Authors

Woo Sup Cho

Sun Gun Chung

Won Kim

Chris H Jo

Shi-Uk Lee

Sang Yoon Lee

Affiliations

Soon will be listed here.

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.

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References

Wohn D . Korea okays stem cell therapies despite limited peer-reviewed data. Nat Med. 2012; 18(3):329. DOI: 10.1038/nm0312-329a. View

Andres B, Murrell G . Treatment of tendinopathy: what works, what does not, and what is on the horizon. Clin Orthop Relat Res. 2008; 466(7):1539-54. PMC: 2505250. DOI: 10.1007/s11999-008-0260-1. View

Nemoto M, Kizaki K, Yamamoto Y, Oonuma T, Hashizume K . Tenascin-C Expression in Equine Tendon-derived Cells During Proliferation and Migration. J Equine Sci. 2014; 24(2):17-24. PMC: 4013982. DOI: 10.1294/jes.24.17. View

Egger M, Davey Smith G, Schneider M, Minder C . Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997; 315(7109):629-34. PMC: 2127453. DOI: 10.1136/bmj.315.7109.629. View

Pascual-Garrido C, Rolon A, Makino A . Treatment of chronic patellar tendinopathy with autologous bone marrow stem cells: a 5-year-followup. Stem Cells Int. 2012; 2012:953510. PMC: 3246763. DOI: 10.1155/2012/953510. View

Kinnaird T, Stabile E, Burnett M, Shou M, Lee C, Barr S . Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation. 2004; 109(12):1543-9. DOI: 10.1161/01.CIR.0000124062.31102.57. View

Liao G, Choi Y, Vojnits K, Xue H, Aroom K, Meng F . Tissue Engineering to Repair Diaphragmatic Defect in a Rat Model. Stem Cells Int. 2017; 2017:1764523. PMC: 5592000. DOI: 10.1155/2017/1764523. View

Mazzocca A, McCarthy M, Chowaniec D, Cote M, Arciero R, Drissi H . Rapid isolation of human stem cells (connective tissue progenitor cells) from the proximal humerus during arthroscopic rotator cuff surgery. Am J Sports Med. 2010; 38(7):1438-47. DOI: 10.1177/0363546509360924. View

Barboni B, Russo V, Gatta V, Bernabo N, Berardinelli P, Mauro A . Therapeutic potential of hAECs for early Achilles tendon defect repair through regeneration. J Tissue Eng Regen Med. 2017; 12(3):e1594-e1608. DOI: 10.1002/term.2584. View

10.

Gomes J, da Silva R, Silla L, Abreu M, Pellanda R . Conventional rotator cuff repair complemented by the aid of mononuclear autologous stem cells. Knee Surg Sports Traumatol Arthrosc. 2011; 20(2):373-7. PMC: 3262133. DOI: 10.1007/s00167-011-1607-9. View

11.

Tsikopoulos K, Tsikopoulos I, Simeonidis E, Papathanasiou E, Haidich A, Anastasopoulos N . The clinical impact of platelet-rich plasma on tendinopathy compared to placebo or dry needling injections: A meta-analysis. Phys Ther Sport. 2015; 17:87-94. DOI: 10.1016/j.ptsp.2015.06.003. View

12.

Jo C, Chai J, Jeong E, Oh S, Kim P, Yoon J . Intratendinous Injection of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells for the Treatment of Rotator Cuff Disease: A First-In-Human Trial. Stem Cells. 2018; 36(9):1441-1450. DOI: 10.1002/stem.2855. View

13.

Havlas V, Kotaska J, Konicek P, Trc T, Konradova S, Koci Z . [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. 2015; 82(3):229-34. View

14.

Begg C, Mazumdar M . Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994; 50(4):1088-101. View

15.

Squillaro T, Peluso G, Galderisi U . Clinical Trials With Mesenchymal Stem Cells: An Update. Cell Transplant. 2015; 25(5):829-48. DOI: 10.3727/096368915X689622. View

16.

Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M . Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015; 350:g7647. DOI: 10.1136/bmj.g7647. View

17.

Lee S, Kim W, Lim C, Chung S . Treatment of Lateral Epicondylosis by Using Allogeneic Adipose-Derived Mesenchymal Stem Cells: A Pilot Study. Stem Cells. 2015; 33(10):2995-3005. DOI: 10.1002/stem.2110. View

18.

Lamas J, Garcia-Fernandez C, Tornero-Esteban P, Lopiz Y, Rodriguez-Rodriguez L, Ortega L . Adverse effects of xenogenic scaffolding in the context of a randomized double-blind placebo-controlled study for repairing full-thickness rotator cuff tears. Trials. 2019; 20(1):387. PMC: 6604436. DOI: 10.1186/s13063-019-3504-3. View

19.

Carballo C, Lebaschi A, Rodeo S . Cell-based approaches for augmentation of tendon repair. Tech Shoulder Elb Surg. 2017; 18(3):e6-e14. PMC: 5737795. DOI: 10.1097/BTE.0000000000000132. View

20.

Machova Urdzikova L, Sedlacek R, Suchy T, Amemori T, Ruzicka J, Lesny P . Human multipotent mesenchymal stem cells improve healing after collagenase tendon injury in the rat. Biomed Eng Online. 2014; 13:42. PMC: 4001357. DOI: 10.1186/1475-925X-13-42. View