Mesenchymal Stem Cells as a Cornerstone in a Galaxy of Intercellular Signals: Basis for a New Era of Medicine

Abstract

Around 40% of the population will suffer at some point in their life a disease involving tissue loss or an inflammatory or autoimmune process that cannot be satisfactorily controlled with current therapies. An alternative for these processes is represented by stem cells and, especially, mesenchymal stem cells (MSC). Numerous preclinical studies have shown MSC to have therapeutic effects in different clinical conditions, probably due to their mesodermal origin. Thereby, MSC appear to play a central role in the control of a galaxy of intercellular signals of anti-inflammatory, regenerative, angiogenic, anti-fibrotic, anti-oxidative stress effects of anti-apoptotic, anti-tumor, or anti-microbial type. This concept forces us to return to the origin of natural physiological processes as a starting point to understand the evolution of MSC therapy in the field of regenerative medicine. These biological effects, demonstrated in countless preclinical studies, justify their first clinical applications, and draw a horizon of new therapeutic strategies. However, several limitations of MSC as cell therapy are recognized, such as safety issues, handling difficulties for therapeutic purposes, and high economic cost. For these reasons, there is an ongoing tendency to consider the use of MSC-derived secretome products as a therapeutic tool, since they reproduce the effects of their parent cells. However, it will be necessary to resolve key aspects, such as the choice of the ideal type of MSC according to their origin for each therapeutic indication and the implementation of new standardized production strategies. Therefore, stem cell science based on an intelligently designed production of MSC and or their derivative products will be able to advance towards an innovative and more personalized medical biotechnology.

Role of Exosomal MicroRNAs and Their Crosstalk with Oxidative Stress in the Pathogenesis of Osteoporosis

“…Recently, exosomal miRNAs have been shown to regulate several physiological processes, including the OS response, in OP [20][21][22][23]. Our review seeks to enhance the understanding of the mechanism underlying OP pathogenesis and to lay the foundation for novel theranostic approaches for OP.…”

New Sources, Differentiation, and Therapeutic Uses of Mesenchymal Stem Cells

“…The clinical applications of MSCs are based on their unique stem cell properties, including the secretion of trophic factors and their proangiogenic, anti-inflammatory, immune-modulatory, and anti-oxidative stress activities. However, large-scale expansion of these cells for allogeneic therapies requires minimization of donor-dependent and bioprocess variabilities [ 4 ]. This Special Issue, entitled “New Sources, Differentiation, and Therapeutic Uses of Mesenchymal Stem Cells”, includes eight articles, four of which are review papers that discuss novel sources of MSCs and recent advances in the characterization and applications of MSCs.…”

“…Over the past decade, MSCs have been proposed as a promising therapeutic treatment for various diseases. Many preclinical and clinical studies have described various strategies for effective MSC therapy, including decisions about the most (1) satisfactory cell type for each therapeutic application, (2) satisfactory culture conditions to ensure therapeutic effects, (3) suitable and effective methods for the mass production of these cells, and (4) appropriate functional tests for determining whether these biological products for each therapeutic indication have been developed to overcome the limitations of MSCs, such as heterogeneity and safety and handling issues [ 4 ].…”

“…EVs of the MSC secretome can generate an encouraging alternative for exploiting MSC properties and can be classified as exosomes (30–120 nm in diameter), which originate within endosomal compartments called multivesicular bodies in the cell [ 4 ]. EVs from AD-MSCs have anti-photoaging potential and have been used in subcutaneous injections in mouse models of photoaging [ 9 , 17 ].…”

“…In addition, genetic engineering techniques have been applied to induce insufficient endogenous factors or new proteins directly within MSCs [ 21 ]. Various MSCs have been used with genetic modification technology using RNA viruses, such as lentiviruses and retroviruses, and DNA viruses, including adenoviruses or adeno-associated viruses, and the preclinical results of these studies have been published [ 4 ]. The formation of spheroids that recover cell communication and provide a concertation gradient of external factors depending on the location, as observed in vivo, has been reported.…”