Stem cells are cellular populations with varying degrees of differentiation that can evolve into different cell types. These cells have the ability, under certain conditions, to repair damaged tissues, and it has long been suggested that pluripotent stem cells, with a high degree of differentiation, play a critical role in tissue repair through their ability to differentiate into the target tissue both in vivo and in vitro. Hence, they have been proposed as an effective therapeutic tool for the treatment of a variety of tissue injuries and diseases.

Several studies on stem cells with lower potency and less ability to differentiate, such as multipotent or mesenchymal stem cells (MSCs), have suggested that their tissue repair benefits, upon transplantation, are a direct result of their paracrine effect rather than their ability to differentiate. It has been observed that in damaged tissues and diseased organs, increased levels of damage signals attract MSCs to the site of injury, allowing them to release a plethora of protein mediators that promote the healing process. These secreted paracrine healing mediators consist of growth and angiogenic factors, soluble mediators, cytokines, chemokines, lipid mediators, and extracellular particles, such as exosomes, which trigger anti-apoptotic and healing events that result in tissue renewal. Administration of conditioned media (CM) derived from in vitro cultures of MSCs, containing these MSC secretory products, has been shown to improve the recovery and healing process in a similar way to the administration of MSCs. Thus, CM could be used in cell-free therapies with the advantages of a lower risk of allogeneic cell immune rejection, the avoidance of expensive stem cell transplantation difficulties, and the ability to mass produce on a pharmaceutical scale. Several preclinical and clinical studies have confirmed that the therapeutic effect of MSC-derived CM is a promising strategy for treating a variety of disorders, comparable to the effect of MSC transplantation, suggesting a potential important role in regenerative medicine therapeutics.

This Special Issue aims to present the latest clinical and non-clinical research on MSC-derived CM, covering studies ranging from the pathogenetic mechanisms of MSC-derived CM to its therapeutic interventions. We welcome both original research and review articles, including studies covering the manufacture and characterization of stem cell-derived CM, in vitro studies demonstrating the effect of CM in cell biology and tissue damage, and data obtained from in vivo experimental models and from currently conducted clinical trials, examining the potential therapeutic effect of CM in various disorders.

Potential topics include but are not limited to the following:

• Characterization of stem cell-derived CM
• Manufacture of stem cell-derived CM
• Immunomodulatory properties of stem cell-derived CM
• Anti-inflammatory properties of stem cell-derived CM
• Anti-fibrotic properties of stem cell-derived CM
• Preclinical studies on the effect of CM in damaged tissue
• Preclinical studies on the effect of CM in diseased organs
• Effects of stem cell-derived CM on cancer
• Animal model studies examining the therapeutic potential of stem cell-derived CM
• Clinical trials using stem cell-derived CM in various disorders
• Therapeutic effects of stem cell-derived CM in viral infections
• Non-therapeutic uses of stem cell-derived CM