Osteoarthritis

About

Osteoarthritis (OA) is a chronic, degenerative disease characterized by joint pain, stiffness, limited mobility, effusion and inflammation. It affects articular cartilage, subchondral bone, menisci (in the knee), synovial tissue, tendons, ligaments and muscle surrounding the joint. The pathology of OA is multifactorial with concomitant structural, inflammatory and metabolic changes, and imbalance between the formation and degeneration of chondrocytes and extracellular matrix, leading to progressive destruction of articular cartilage. It has negative physical and psychological impacts resulting in disability and reduced quality of life (1).

The Potential of Mesenchymal Stem Cells (MSCs)

MSCs hold great potential as a novel treatment for osteoarthritis, given their anti-inflammatory, regenerative and immunomodulatory properties.

MSCs help the body repair by creating a regenerative microenvironment that supports and promotes the natural healing of injured tissue. MSCs migrate to injured or inflamed sites in response to environmental signals, and interact with the local microenvironment, primarily by secretion of numerous bioactive molecules and through cell-to-cell contact (2-3). These intricate mechanisms are believed to include the modulation of immune responses and the attenuation of harmful inflammation, promotion of cell survival, stimulation of endogenous progenitor cells and development of new blood vessels in damaged tissue (2-4).

In osteoarthritis, the cartilage in the joints becomes damaged or wears away, leading to pain and stiffness (1). 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 (5–8).

Preclinical and Clinical Trials

The promise of MSCs as a therapeutic modality has been demonstrated in a number of preclinical studies and in clinical setting. Studies have shown that intra-articular injection of MSCs may reduce joint inflammation and may be able to promote cartilage regeneration, improving function of OA joints (5–8).

Randomized double–blind phase I/II clinical studies have reported clinical, radiological and histological improvement in OA patients. These studies demonstrate the safety and tolerability of MSC treatment, with no serious adverse events observed (5-7).

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 OA (5). The authors reported positive effects of MSCs in mitigating pain and symptoms, improved quality of life, and evidence of structural improvements or cartilage preservation. No serious adverse events were reported.

Based on the preclinical and clinical data available in the literature, our clinical trial is designed to evaluate the safety, tolerability and efficacy of intra-articular human allogeneic bone marrow-derived MSC in osteoarthritis.

  1. Martel-Pelletier, Pathophysiology of osteoarthritis, Osteoarthritis and Cartilage, Volume 12, Supplement, 2004, Pages 31-33, ISSN 1063-4584, https://doi.org/10.1016/j.joca.2003.10.002.

2. 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.

3. 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.

4. 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.

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. Wang G, Xing D, Liu W, Zhu Y, Liu H, Yan L, Fan K, Liu P, Yu B, Li JJ, Wang B. Preclinical studies and clinical trials on mesenchymal stem cell therapy for knee osteoarthritis: A systematic review on models and cell doses. Int J Rheum Dis. 2022 May;25(5):532-562. doi: 10.1111/1756-185X.14306. Epub 2022 Mar 4. PMID: 35244339