The use of mesenchymal stem cells (MSCs) in orthopaedics has encountered a large rise in the last decade, to treat disparate degenerative diseases, such as tendinopathies, muscle injuries and osteoarthritis. Despite some clinical trials having already been published, the application of MSCs is subject to a number of variables that should be carefully considered: the different harvest sites and the inherent biologic differences existing, the manipulation process to obtain MSCs (minimal or extensive), and the application modalities and therapeutic protocols.

There are relevant procedural, regulatory and ethical aspects concerning the application of MSCs. Firstly, there is ongoing in vitro and animal research to understand the mechanisms of action of MSCs in different musculoskeletal tissues, which is fundamental to provide patients with reliable information on what to expect from MSCs application for a specific pathology. Furthermore, many harvest sites and harvest techniques have been described, employing different devices and different preparation methods, ranging from minimal manipulation (i.e. centrifugation or mechanical separation) to cell expansion in the lab. Lastly, different therapeutic protocols have been tested and strategies to enhance the outcomes of MSCs have been attempted, such as biologic adjuvants, biomaterials, and scaffolds.

Amid this rapidly evolving scenario, there is the need of summarising the available evidence. Therefore, the aim of this Special Issue is to collate both original and review articles that shed light on the role of MSCs in the treatment of musculoskeletal conditions and on how to safely and effectively adopt this novel biologic strategy. We aim to solicit submissions from both clinicians without experience in the field able to collect all the essential data to properly inform patients and decide on a preferred approach, as well as from experienced clinician who can report the most updated news on the topic and future trends of research. Furthermore, we also welcome submissions that address regulatory and ethical concerns, including understanding rules and limitations existing among different countries as this is mandatory to guarantee the safety of the patient and to ensure adherence to the best standard of care and research.

Potential topics include but are not limited to the following:

• In vitro and animal studies on MSCs in orthopaedics
• Source of MSCs for orthopaedic application
• Biologic actions of MSCs in osteoarthritis
• Biologic actions of MSCs towards tendon and muscle tissues
• MSCs harvest strategies
• MSCs manipulation process (minimal vs extensive and novel approaches)
• Application modalities
• Strategies to increase the efficacy of MSCs (adjuvants, scaffold, biomaterials)
• Clinical studies dealing with results of application of MSCs
• Insights on regulatory and ethical aspects regarding the use of MSCs
• Future trends in the field of MSCs in orthopaedics