Osteoarthritis (OA) is a leading cause of disability affecting 600 million people worldwide. Characterised by joint-wide inflammation and structural damage, OA causes chronic pain and significantly impairs the patient’s ability to perform daily activities. Despite having huge socioeconomic consequences, OA has no cure.
Currently, all available treatments for OA focus on relieving pain, with little effect on slowing disease progression. Driven by the urgent need for a new solution, stem cell therapies have recently emerged, among which mesenchymal stem cells (MSCs) have been the most commonly tested due to their natural anti-inflammatory and restorative functions [1]. However, despite positive results obtained in preclinical studies, existing clinical trials using MSC injections to treat knee OA have not demonstrated consistent benefits [2].
The efficacy of MSC therapy for clinical OA treatment is limited by some key factors: (1) variation in the characteristics of MSCs derived from different tissue sources, (2) inevitable loss or death of a majority of cells after injection, (3) suboptimal function of cells grown using traditional 2D culture methods. Our team has investigated strategies to address each of these challenges, by (1) experimenting with more pluripotent sources of MSCs (e.g., derived from umbilical cord or embryonic stem cells), (2) using microcarrier systems to enable more efficiency delivery into the joint and greater cell viability after injection, (3) optimising 3D culture methods to enhance MSC paracrine activity.
Interestingly, our recent work also demonstrated that live MSCs may adopt the diseased characteristics of the OA joint after injection, hence reducing their long-term therapeutic benefits [3]. This has prompted us to look into harnessing the MSC secretome to generate cell-derived bio-therapeutics as a new-generation treatment option for OA. We hope that our combined therapeutic discovery strategy can in the future be adapted for other types of chronic diseases.
References:
[1] G. Wang, D. Xing, W. Liu, Y. Zhu, H. Liu, L. Yan, K. Fan, P. Liu, B. Yu, J. J. Li, B. Wang, International Journal of Rheumatic Diseases, 2022, 25, 532-562.
[2] Z. Shang, P. Wanyan, B. Zhang, M. Wang, X. Wang, Stem Cell Research & Therapy, 2023, 14: 91.
[3] V. Shang, J. Li, C. B. Little, J. J. Li, European Cells & Materials, 2023, 45: 143-157.