In the field of Regenerative Medicine, the preclinical and clinical research on multipotent adult stem cells, and in particular mesenchymal stem cells (MSCs), has prompted the identification of new therapeutic approaches for the treatment of structural tissue/organ dysfunctions and congenital or acquired diseases. Over the last decades, compelling evidence has demonstrated that the powerful therapeutic effects of MSCs are due to paracrine-like secretion of cytokines (growth factors and chemokines) and extracellular vesicles (EVs). EVs are the paracrine effectors of MSCs, that carry a set of molecules capable of influencing the metabolism and even the phenotype of target cells/tissues.

The application of MSCs as biological drugs in cell therapy is based on regulating the inflammatory response and participating in tissue repair and regeneration. The therapeutic effect of MSCs is largely ascribed to their immunomodulatory function regulated by the inflammatory environment. Among the most important regenerative properties and immune regulation capabilities of MSCs is the secretion of EVs that retain the therapeutic action of the parent cells. The use of EVs may help to overcome the safety concerns associated with live cell therapy and become the focus of future clinical approaches in Regenerative Medicine.

Several researchers have explored the role of MSCs and MSC-EVs in various tissue-damaging diseases. However, their key role in the development of immune regulation and stimulation of tissue regeneration still deserves to be clarified prior to their clinical application.

This Research Topic invites different kinds of contributions (e.g., original research articles, short communications, review articles, clinical studies) that focus on the preclinical and translational investigation of MSCs and MSC-EVs about different therapeutic aspects related to organ/tissue regeneration.

Topics include, but are not restricted to the following:

•MSC responsiveness to humoral and mechanical stimuli to promote functional tissue regeneration
•Interactions between MSCs and natural/synthetic biomaterials for the development of advanced tissue substitutes
•Standardization of MSC-EV isolation and enrichment techniques and characterization of their biological structure, transcriptome and secretome
•In vitro and in vivo investigation of the paracrine activity of MSCs and MSC-EVs, including their immunomodulatory function
•MSC and MSC-EV based therapies in animal models of organ failure and disease

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Frontiers in Pharmacology

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