Musculoskeletal Injuries and Degeneration

About

Musculoskeletal disorders include a range of medical conditions affecting the systems of bones, joints, muscles, ligaments, tendons, and other supportive structures of the human body.

Musculoskeletal Disorders

Musculoskeletal disorders (MSDs) include acute injuries, chronic conditions and degenerative and inflammatory diseases. Injuries to firm connective tissues, such as cartilage and bone, can result in significant functional impairments, and conditions like osteoarthritis can arise from the cartilage damage. Soft connective tissue injuries or inflammation, involving ligaments, tendons, and muscles, can stem from trauma or overuse, leading to pain and reduced function. Degenerative changes in both firm and soft connective tissues are often linked to ageing, chronic inflammation and repetitive strain. Although physical exercise is useful in preventing and managing these conditions, the pain and mobility often limit individuals from engaging in physical activities and significantly affects their general health and quality of life [1].

The Therapeutic Potential of MSCs

MSCs hold great potential as a novel treatment for MSDs, given their anti-inflammatory, regenerative and immunomodulatory properties. Numerous experimental studies have shown that both local and systemic administration of MSCs suppresses detrimental immune responses in inflamed tissues and promotes tissue repair [2]. MSCs have been shown to migrate to sites of injury and inflammation in response to environmental signals, where they interact with the local microenvironment, primarily by secretion of numerous bioactive molecules and through cell-to-cell contact [3-4]. The intricate mechanisms of MSCs are believed to include modulating the immune response to attenuate harmful inflammation and promote regeneration, rescuing injured cells and promoting cell survival, stimulating endogenous progenitor cells and inducing new blood vessels in damaged tissue [3-4]. In osteoarthritis, the cartilage in the joints becomes damaged or wears away, leading to pain and stiffness. Studies indicate that MSCs may be able to stimulate repair or regeneration of cartilage cells, which could help heal damaged cartilage and improve symptoms of osteoarthritis [5-7].

Clinical Evidence

The therapeutic potential of MSCs in treatment of musculoskeletal disorders has gained significant clinical attention. Preclinical and clinical studies indicate that MSCs may be effective in treating conditions like osteoarthritis, cartilage defects, rheumatoid arthritis, degenerative disc disease and tendon disorders [5-10]. A review article published in 2023 evaluated 15 randomized controlled clinical trials (RCTs) and 11 nonrandomized clinical trials, with a sample size of 610 patients, using MSCs in the treatment of knee osteoarthritis. The authors reported positive effects in mitigating pain and symptoms, improved quality of life, and evidence of structural improvements or cartilage preservation. No serious adverse events were reported [5]. The efficacy and safety of MSC therapy in patients with tendon disorders was assessed in 2021 by Cho et al. in a systematic review and meta-analysis of four prospective clinical studies. The study showed a significant overall improvement in pain, function, and radiological and arthroscopic parameters in patients with tendon disorders [10]. Based on the preclinical and clinical data available in the literature, our clinical trial is designed to evaluate the safety, tolerability and efficacy of local and/or systemic injections of human allogeneic bone marrow-derived MSC in musculoskeletal injury and degeneration.

1. Vigorita, V.J., 2008. Orthopaedic pathology. Lippincott Williams & Wilkins.

2. Krampera M, Le Blanc K. Mesenchymal stromal cells: Putative microenvironmental modulators become cell therapy. Cell Stem Cell. 2021 Oct 7;28(10):1708-1725. doi: 10.1016/j.stem.2021.09.006. PMID: 34624232.

3. Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell. 2011 Jul 8;9(1):11-5. doi: 10.1016/j.stem.2011.06.008. PMID: 21726829; PMCID: PMC3144500.

4. Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp Mol Med. 2013 Nov 15;45(11):e54. doi: 10.1038/emm.2013.94. PMID: 24232253; PMCID: PMC3849579.

5. Copp G, Robb KP, Viswanathan S. Culture-expanded mesenchymal stromal cell therapy: does it work in knee osteoarthritis? A pathway to clinical success. Cell Mol Immunol. 2023 Jun;20(6):626-650. doi: 10.1038/s41423-023-01020-1. Epub 2023 Apr 25. PMID: 37095295; PMCID: PMC10229578.

6. Kangari P, Talaei-Khozani T, Razeghian-Jahromi I, Razmkhah M. Mesenchymal stem cells: amazing remedies for bone and cartilage defects. Stem Cell Res Ther. 2020 Nov 23;11(1):492. doi: 10.1186/s13287-020-02001-1. PMID: 33225992; PMCID: PMC7681994.

7. Ha C-W, Park Y-B, Kim SH, Lee H-J. Intra-articular mesenchymal stem cells in osteoarthritis of the knee: a systematic review of clinical outcomes and evidence of cartilage repair. Arthroscopy. 2019;35(1):277-288.e2.

8. Sarsenova M, Issabekova A, Abisheva S, Rutskaya-Moroshan K, Ogay V, Saparov A. Mesenchymal Stem Cell-Based Therapy for Rheumatoid Arthritis. Int J Mol Sci. 2021 Oct 27;22(21):11592. doi: 10.3390/ijms222111592. PMID: 34769021; PMCID: PMC8584240.

9. Xie, B., Chen, S., Xu, Y., Han, W., Hu, R., Chen, M., He, R. and Ding, S., 2021. Clinical efficacy and safety of human mesenchymal stem cell therapy for degenerative disc disease: A systematic review and meta-analysis of randomized controlled trials. Stem Cells International, 2021.

10. Cho, W.S., Chung, S.G., Kim, W., Jo, C.H., Lee, S.U. and Lee, S.Y., 2021. Mesenchymal stem cells use in the treatment of tendon disorders: a systematic review and meta-analysis of prospective clinical studies. Annals of rehabilitation medicine, 45(4), p.274.