Stem cell therapies have expanded in use over the last 30 years, and are now widespread. Substituting extracellular vesicles for the stem cells is a more recent innovation, but also now widely used in the medical tourism industry. These treatments have shown effects on aging and longevity in animal studies, but we have no idea whether this is the case in humans, and we are in no danger of finding out any time soon. Even short clinical trials are expensive, while trials large enough and long enough to assess effects on life span are prohibitively expensive. There is as yet no generally accepted and trusted measure of biological age one might apply to patients before and after a treatment. The existing aging clocks will produce their results, but those results have yet to be calibrated against real-world outcomes for life span.
One is only left with the reasonable hypothesis that reducing chronic inflammation and encouraging tissue maintenance via this class of therapy will slow the progression of aging to some degree. How much of a degree? No-one knows. One pessimistic view of the field of rejuvenation biotechnology as a whole is that the recent history of stem cell medicine is a preview of the next 30 years of efforts to treat aging, in that (a) useful therapies will slowly spread into widespread clinical use, but (b) we will have no concrete measure as to how effective these therapies are when it comes to slowing or reversing aging.
With all of this in mind, today's open access paper provides a discussion of stem cell therapies and extracellular vesicle therapies from the point of view of the treatment of aging, rather than the treatment of specific conditions per se. As the authors point out, there is ample data to characterize the safety of these treatments and the beneficial suppression of inflammation produced by these treatments, but next to nothing can be said about how the observed effects on life span in animal models translate to humans.
Mesenchymal stem cells and their derivatives as potential longevity-promoting tools
Mesenchymal stem cells (MSCs) represent a distinct population of mesenchymal stromal cells, which (i) are able to adhere to plastic surfaces, (ii) express specific cell surface markers (CD73, CD90, and CD105, but not CD14, CD34, CD45, and HLA-DR), (iii) and are able to differentiate into osteogenic, chondrogenic, or adipogenic cell lineages in vitro. It should be noted that MSC isolation yields heterogeneous, non-clonal cultures of stromal cells, including stem cells with diverse multipotent potential, committed progenitors, and differentiated cells. MSCs are found in virtually all organs of the adult organism, examined thus far. A rapidly growing body of evidence indicates the beneficial effects of systemic administration of MSCs or MSC-derived extracellular vesicles (EVs) in various pathological conditions, including age-related diseases (ARDs). For example, the systemic administration of bone marrow-derived MSCs or MSC-derived EVs from young rodents increased hippocampal neurogenesis and improved cognitive function in aged animals.
Systemic administration of MSCs and stem cell/blood-derived EVs modified the omics profiles of various organs of aged rodents towards the young ones. The application of EVs appears to be even more beneficial than MSCs. Remarkably, over 70% of microRNAs, which are over-presented in ESC-derived EVs, were found to target longevity-associated genes. Along with MSCs, other types of stem cells were reported to display healthspan- and lifespan-extending effects. Pluripotent Muse cells, a specific subpopulation of MSCs, which possess a number of unique features, could be particularly relevant for promoting healthspan. The rejuvenation potential of MSCs, EVs, and Muse cells warrants further investigation in both animal models and clinical trials, using aging clocks for biological age determination as one of the endpoints.
Longevity is the most general and integrative parameter for evaluating the therapeutic effects of any interventions. Another integrative parameter directly related to life expectancy is biological age. Recently, its determination has become possible, using various biological aging clocks. However, to date, a comprehensive analysis of the impact of MSCs/MSC-derived EVs on longevity, biological age, and aging phenotypes has not been conducted. With this in mind, in this review, we primarily focus on the effects of MSC or EV administration on the lifespan of wild-type or progeroid animals. Along with the health- and lifespan-extending effects, we discuss their putative mechanisms as well as the impact on biological age and aging omics signatures.