Adipose-derived stem cells (ASCs) secrete many cytokines, proteins, growth factors, and extracellular vesicles with beneficial outcomes that can be used in regenerative medicine. It has great potential, and the development of new treatment strategies using the ASCs secretome is of global interest. Besides cytokines, proteins, and growth factors, the therapeutic effect of secretome is hidden in non-coding RNAs such as miR-21, miR-24, and miR-26 carried via exosomes secreted by adequate cells. The whole secretome, including ASC-derived exosomes (ASC-exos) has been proven in many studies to have immunomodulatory, proangiogenic, neurotrophic, and epithelization activity and can potentially be used for neurodegenerative, cardiovascular, respiratory, inflammatory, and autoimmune diseases as well as wound healing treatment. Due to limitations in the use of stem cells in cell-based therapy, its secretome with emphasis on exosomes seems to be a reasonable and safer alternative with increased effectiveness and fewer side effects. Moreover, the great advantage of cell-free therapy is the possibility of biobanking the ASCs secretome. In this review, we focus on the current state of knowledge on the use of the ASCs secretome in stem cell-free therapy.

Globally, osteoporosis is the most common systemic skeletal disease. There are many factors that influence osteoporosis’ development and progression. During the pathogenesis of this disease, bone turnover is imbalanced between resorption and the formation of bone tissue. A growing interest has been devoted to the role that microRNA (miRNA) plays in osteoporosis regulation. A microRNA (miRNA) is a group of small single-stranded RNA molecules involved in regulating gene expression in eukaryotic organisms. As microRNAs (miRNAs) are key regulators of gene expression and can modulate processes related to bone metabolism, they have become increasingly important for studying osteoporosis pathogenesis. The available research suggests that miRNAs play an important role in regulating processes associated with bone metabolism, especially by influencing bone resorption and synthesis. Furthermore, microRNAs can also serve as potential therapeutic targets for osteoporosis, besides being a rapid and specific biomarker.

Adipose-derived stem cells (AT-MSCs) exhibit great potential for application in stem cell therapy, primarily due to their unique pro-regenerative capabilities, which include supporting skin regeneration. AT-MSCs secrete a variety of biomolecules with immunomodulatory, re-epithelializing, antifibrotic, antiapoptotic, proangiogenic, and neurotrophic activity as well as the ability to promote proliferation and migration of skin cells. Recently, therapy using AT-MSC secretome alone has garnered increasing attention due to its potentially safer and more effective application ability than the use of whole AT-MSCs. This review provides a comprehensive summary of the current state of knowledge regarding the potential use of AT-MSC secretome as a promising cell-free therapeutic strategy for wound healing, alopecia, skin rejuvenation, and skin inflammatory diseases. We critically analyze and discuss findings from in vitro, in vivo, and clinical studies. Moreover, we briefly discuss possible approaches to enhance the secretion of AT-MSC biomolecules, such as AT-MSC preconditioning with low-frequency electromagnetic fields and hypoxia. In conclusion, the evidence presented in this review paper underscores that the AT-MSC secretome alone can be a highly effective approach as a stem cell-free therapy for skin repair, with significant translational potential.

Mesenchymal stem cells (MSCs) offer great potential for use in stem cell-based therapies due to their unique regenerative potential via reconstructive and paracrine capacities. These therapies offer new hope for patients suffering from conditions that have no cure. Currently, mesenchymal stem cells (from adipose tissues, bone marrow, and umbilical cords) are most interesting for application in those therapies. Nevertheless, the development of MSC-based medical products requires thorough research and standardization that maximizes the therapeutic effect while minimizing side effects. One of the interesting novel approaches to achieving this goal is combining MSC therapy with an electromagnetic field (EMF). Many studies have shown that EMF can enhance the regenerative properties of MSCs by influencing stem cell fate through modulating differentiation, proliferation, cell cycle regulation, metabolism, and cytokine and growth factor secretions. Combination therapy of EMF-MSCs is a promising perspective; however, it is important to select appropriate EMF parameters to obtain beneficial therapeutic effects. Therefore, understanding the mechanisms involved in the EMF impact on MSCs is crucial. In this study, we provide an overview of the effects of EMF on the biological response and “fate” of MSCs, paying attention to the gaps in research that remain unfilled and discuss the clinical application of this approach.

Adipose-derived stem/stromal cells (ASCs) have tremendous potential for use in regenerative medicine; their secretome is especially important for regenerative processes. We hypothesized that exposure of ASCs to an electromagnetic field (EMF) can influence the proregenerative potential of cells by influencing the secretion of growth factors (GFs) responsible for regenerative properties. We showed that the exposure of ASCs to an EMF (50 Hz; 1.5mT) affected the secretion of GFs as well as the cell cycle process. The most important observation was a statistically significant, 3-fold increase in FGF-2 concentration at 48 h, and a 2-fold decrease at 72 h when compared to the control group. This finding is very important for regenerative medicine, because with precisely adjusted parameters, an EMF can be used to stimulate the production of GFs, mainly of FGF-2, by ASCs, thereby increasing proregenerative properties. The ASC secretome after EMF treatment could be a method for easy, simple and costeffective stem cell differentiation and therapy facilitation.