Cartilage repair by mesenchymal stem cells: Clinical trial update and perspectives

Abstract

Osteoarthritis is a degenerative disease of joints with destruction of articular cartilage associated with subchondral bone hypertrophy and inflammation. OA is the leading cause of joint pain resulting in significant worsening of the quality-of-life in the elderly. Numerous efforts have been spent to overcome the inherently poor healing ability of articular cartilage. Mesenchymal stem cells (MSCs) have been in the limelight of cell-based therapies to promote cartilage repair. Despite progressive advancements in MSC manipulation and the introduction of various bioactive scaffolds and growth factors in preclinical studies, current clinical trials are still at early stages with preliminary aims to evaluate safety, feasibility and efficacy. This review summarises recently reported MSC-based clinical trials and discusses new research directions with particular focus on the potential application of MSC-derived extracellular vehicles, miRNAs and advanced gene editing techniques which may shed light on the development of novel treatment strategies. The translational potential of this article: This review summarises recent MSC-related clinical research that focuses on cartilage repair. We also propose a novel possible translational direction for hyaline cartilage formation and a new paradigm making use of extra-cellular signalling and epigenetic regulation in the application of MSCs for cartilage repair.

Keywords: MSCs; epigenetics; osteoarthritis; secretome; translation.

Figure 1

Schematic illustration of the proposed strategy of hyaline cartilage regeneration with MSCs and secreted EVs. Naïve or genetically modified MSC-secreted EVs consisting of bioactive proteins and miRNAs could be used directly to modulate the microenvironment of the damaged cartilage tissue to promote cartilage repair, or be used to enhance the chondrogenic ability of the primed MSCs before injection or implantation for cartilage repair.