Analysis of MSCs' secretome and EVs cargo: Evaluation of functions and applications

Mesenchymal stem cells (MSCs) can exert different functions and can be used in several medical fields. In the last years, MSC properties have been attributed to their secreted factors such as soluble proteins, cytokines and growth factors. Moreover, a key role is played by the extracellular vesicles (EVs) which lead a heterogeneous cargo of proteins, lipids and small and long non-coding RNAs that interfere with the pathways of the recipient cells. Due to the safeness and easiness in obtaining the secretome, its use is becoming a turning point for the application in physiological and pathological fields. This review summarizes the most recent studies on the use of MSCs secretome, focusing on some physiological (angiogenesis and osteogenesis) and pathological (cancer, cardiovascular and autoimmune diseases) applications. The secreted analyzed factors are listed in a table. In addition, the different characteristics of the fetal MSCs derived secretome and the differences in the secretome composition of three-dimensionally (3D) cultured cells are discussed. As very innovative aspects, recent studies on some applications of engineered vesicles, embedded or not in three-dimensional structures, are treated and the influence of some epigenetic modifications on cells and EVs is investigated.