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.
Highlights
Despite advances in medicine, there are still shortcomings in the treatment of many inflammatory, degenerative, or cancerous diseases, for which there is no curative treatment option
We count on the novel paradigms of science and medicine, which will contribute to glimpsing new solutions for old problems and for emerging challenges that will arise in the future
For example, extracellular vesicles (EVs) from human UC-mesenchymal stem cells (MSC) reverse the development of bladder carcinoma cells, possibly by downregulating the phosphorylation of Akt protein kinase and upregulating cleaved caspase-3 [71], with exosomal miRNA from adipose-derived MSC (AD-MSC) suppressing the proliferation of ovarian cancer cells [72]
Summary
There are still shortcomings in the treatment of many inflammatory, degenerative, or cancerous diseases, for which there is no curative treatment option. To this we must add that, at present, the social demand to find treatments for a gradually wide spectrum of rare diseases is increasing To this cocktail of urgent needs, we must add the problem of infections (especially due to the looming crisis of resistance of many bacterial strains to antibiotics), the emergence of new pandemics (such as that caused by the coronavirus), and the dramatic and progressive increase in average life expectancy throughout the world population. Hope is focused on MSC, observing an exponential increase in research based on them [1] This is due to their influence in many basic aspects of cell biology, making a multifaceted therapeutic approach possible and breaking the classic concept of the pharmaceutical industry of “one disease: a single therapeutic target” [2]. Others such as fetal/neonatal tissues [8,9,10,11], dental pulp [12], or placenta [8] are becoming of increased interest
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