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

Abstract

SummaryOsteoarthritis 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.

5‐Azacytydine and resveratrol reverse senescence and ageing of adipose stem cells via modulation of mitochondrial dynamics and autophagy

“…Due to their unique properties, ASCs hold promise in treating multiple disorders, including graft versus host disease, multiple sclerosis, diabetes mellitus and autoimmune‐induced diseases . Moreover, their application in bone and cartilage regeneration as well as wound healing was widely investigated . There has been a growing number of ASC‐related studies demonstrating the ability of these cells to decrease IR, promote regeneration of pancreatic beta cells and suppress autoimmunity in the course of diabetes …”

Emerging Interventions for Elderly Patients—The Promise of Regenerative Medicine

“…Some early studies suggest that intra‐articular injections of MSCs may be of benefit in OA of the knee, although it is unclear whether the MSCs result in cartilage regeneration or whether the anti‐inflammatory effect of MSCs may explain the observed clinical benefit . A recent systematic review of stem cell therapy in OA suggested that, although the published literature suggests a benefit of this MSC, there is limited high‐quality evidence and long‐term follow‐up for these therapies in OA …”

Therapeutics of Stem Cell Treatment in Anti-Aging and Rejuvenation

“…Collagen is hyaline cartilage composed of 60% (by dry weight) chondrocytes. Fibrocartilage and elastic cartilage are two other types of cartilage differing in ECM and cell components [115].…”

“…As the matrix decreases, articular cartilage becomes increasingly thin, the hydration of cartilage decreases, and the number of cartilage cells also decreases [115].…”

“…Most previous studies have focused on the clinical benefits of MSC treatment, regardless of the source of the cells, the indications, or the mode of administration [114]. MSCs have been used in cell therapy to promote the repair of cartilage, muscle, or bone [115]. These cells are typically harvested from bone marrow and are characterized according to the stimulatory factors they provide [118].…”