Reviewing the Ongoing Move from Stem Cell Therapies to Exosome Therapies
The medical tourism industry has adopted the therapeutic use of exosomes derived from stem cells in much the same way as it adopted the use of stem cell therapies. Transplanted stem cells produce benefits via signaling, and most signaling is carried via extracellular vesicles such as exosomes. From a logistics point of view, exosomes are more easily stored, transported, and used, while all of the tools needed to harvest exosomes from stem cell cultures already existed. Meanwhile, the regulated medical industry lags years behind, given the large costs and lengthy development programs required to satisfy regulatory requirements for manufacturing consistency and data on outcomes. Lack of consistency is certainly a long-standing issue in stem cell therapies, and will likely continue to be an issue for exosome therapies. This may simply be an inherent characteristic of material sourced from donors, and will continue to exist until such time as standardized universal cell lines are a going concern.
Stem cell-derived exosomes have broad application prospects in different medical fields, and are increasingly being considered a replacement for mesenchymal stromal cells (MSCs) therapy. Adipose-derived stem cells (ADSCs) are an efficient and high-quality source of stem cell exosomes because ADSCs can be easily obtained from autologous adipose tissue and there are only minor ethical concerns, also ADSCs shown multipotent differentiation potential, self-renewal potential, low immunogenicity, and high proliferation rate.
Exosomes derived from ADSCs have the function of promoting tissue regeneration through activation or inhibition of multiple signaling pathways (such as Wnt/β-catenin, PI3K/Akt), and immunomodulation, angiogenesis, cell migration, proliferation and differentiation, and tissue remodeling. This review presents the current state of knowledge on ADSCs exosomes and summarizes the use of ADSCs exosomes in stem cell-free therapies for the treatment of diabetes mellitus, cardiovascular, wound healing, neurodegenerative, skeletal, respiratory diseases, and skin aging and other conditions, thus providing novel insights into the clinical applications of MSC-derived exosomes in disease management.
Hi Reason. The article that is the basis for your comment is focused on exosomes derived from adipose-derived stem cells, and your comment refers to exosomes derived from stem cells in general, giving the impression (specially for the title) that exosomes are kind of a continuation of the use of stem cells, without any significant theoretical change, as it would just mean that the healing effect of stem cells happens through the exosomes they release. However, there are many recent studies that show that therapeutic exosomes can be derived not just from stem cells, but also from the blood plasma, and that the exosomes derived from young blood plasma are more effective than those derived from old plasma. I will put a list of these studies at the end of this comment. So the use of exosomes is not just a continuation of the use of stem cells. First, because if therapeutic exosomes can be extracted from blood plasma, this is a far abundant and cheaper source than stem cells - specially if this blood plasma can be from another mammal species, as several studies indicate. Also, if exosomes from young blood plasma are able to rejuvenate mammals, it can indicate a theoretical difference from the rationale of using stem cells (or their exosomes) to repair damage, to the rationale of using exosomes to implement a younger age-phenotype of the body through signaling, which would mean a way to reverse aging through signaling (which then would lead to damage repair via cells' self-repair after they receive the command - the signaling - to do it), instead of trying to repair the damage directly. So, it would mean that there is an upstream biological phenomenon before the accumulation of damage in aging, which would be the signaling (in the blood stream and other tissues) that indicates which degree of damage accumulation the body should have (its age-phenotype). By the way, that's the idea behind the reproduction of Katcher's seminal experiment that we are carrying out here in Brazil - the 67% epigenetic rejuvenation of the rats can't be left there; we need to clarify it immediately, precisely because it makes sense, taking into account many studies published in the last few years. The link to the studies to which I referred previously in this comment are the following: https://www.nature.com/articles/s43587-024-00612-4 , https://www.dovepress.com/small-extracellular-vesicles-from-young-healthy-human-plasma-inhibit-c-peer-reviewed-fulltext-article-IJN , https://www.sciencedirect.com/science/article/pii/S2452199X25001148 , https://www.tandfonline.com/doi/full/10.1080/10790268.2023.2274637 , https://journals.physiology.org/doi/full/10.1152/ajpcell.00022.2025 , https://pubmed.ncbi.nlm.nih.gov/40285735/ , https://www.sciencedirect.com/science/article/pii/S1043661825000167 .
Hi Nicolás,
I don't think we should pit exosomes derived from stem cells against those found in blood plasma. After all, the latter are produced somewhere in the body, and it's quite possible that this is done at least in part by stem cells. Therefore, I believe the two research avenues are complementary.
Furthermore, to say that extracting exosomes from animal blood is a much more efficient and cheaper method than using stem cells is to overlook all the ethical and environmental problems that this raises if we consider it on a large scale.