The musculoskeletal system – which is composed of cartilage, bone, muscle, tendon, and ligament – provides support, stability, and movement to our body. Musculoskeletal disorders, such as osteoarthritis, rheumatoid arthritis, osteoporosis, osteosarcoma, and sarcopenia, etc., have poor outcomes and current treatment options are limited. Nevertheless, the development of stem cell-based therapy has brought a new future for the treatment of musculoskeletal disorders over the past few decades.

Musculoskeletal stem/progenitor cells (MSSPs) are involved in the development, homeostasis, and regeneration of the musculoskeletal system. For example, the articular cartilage progenitors, which reside in the superficial zone of the articular cartilage, likely generate underlying articular chondrocytes to form the entire articular cartilage. Similarly, the cells in resting zone of the postnatal epiphyseal growth plate cartilage cycle slowly and yield underlying chondrocytes. Moreover, the subpopulations of tendon progenitor cells have also been identified as Tppp3+Pdgfra+ and Nes+Scx+ cells. The microenvironment (also known as niche) where MSSPs reside in vivo influences their self-renewal and differentiation fate. The niche regulators include surrounding cells, the extracellular matrix, physical factors (oxygen tension and mechanical load, etc.), and local gradients of cytokines. Knowledge about the mechanisms behind the phenotype maintenance and directional differentiation of MSSPs, and the re-establishment of a functional and therapeutic MSSPs niche, is important for translational medicine for the treatment of musculoskeletal disorders.

The aim of this Special Issue is to consolidate our understanding of MSSPs, from basic biology to translational medicine. We welcome the submission of original research and review articles related to MSSPs in musculoskeletal disorders.

Potential topics include but are not limited to the following:

• MSSPs-based therapy for musculoskeletal disorders with special interest in methods that can simulate endogenous MSSPs
• Novel molecular mechanisms, mechanical stimuli, and biomaterial design for the directional differentiation of MSSPs in vivo and in vitro
• MSSPs phenotype maintenance and aging in physiological and pathological conditions of the musculoskeletal system
• MSSPs interactions with the microenvironment in physiological and pathological conditions of the musculoskeletal system
• Fate determination of MSSPs during musculoskeletal system development
• Identity and subpopulation of novel MSSPs
• Application of mesenchymal stem cells-based therapy (extracted from bone marrow, adipose tissue, placenta, or other organs) for musculoskeletal disorders