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Reviewed by Inna Gordiienko, biologist of biotechnology laboratory, PhD.
Written by Viktoria Kosiak, biologist assistant, biophysicist
We have already talked about what are exosomes and what are the prospects of their application in medicine. In this article, we will talk about exosomes derived from mesenchymal stem cells (MSCs). What are their advantages and disadvantages? What diseases exosomes are used to treat? Please read in this article.
Mesenchymal stem cells are multipotent adult stem cells that can give rise to different types of connective tissue cells. In other words, such a stem cell can be transformed into differentiated cells of bone, cartilage, skin, internal organs and blood vessels. Regeneration of the organism is thanks to stem cells.MSC is the type of stem cells that is most often used in cell therapy of various diseases. They can be obtained from various sources, such as bone marrow, adipose tissue, placenta, umbilical cord, etc. Please read more about treatment programs using MSCs here.
The therapeutic effect of MSCs is realized in two main ways:1. Direct — replacement of damaged cells with transplanted MSCs.2. Indirect or paracrine — secretion of a wide variety of biologically active substances of MSCs after transplantation, such as growth factors, cytokines, hormones and extracellular vesicles, including exosomes.
The second way dominates among them. Many current studies show that exosomes derived from stem cell have similar functions to parent cells. The structure of exosomes obtained from MSCs varies considerably and depends on the tissue source of MSCs. More than 150 different miRNAs and more than 850 unique proteins in MSC exosomes have been identified.That is why regenerative medicine is not limited to the use of cells. Exosomes can also restore the body on their own. Please follow the link and learn more about other cellular products used in regenerative medicine: Good Cells Products.
MSC exosomes have a broad therapeutic potential. Today, a number of preclinical and clinical studies are in process to determine the effectiveness of exosomes in the treatment of the following diseases:
● fatty liver disease;● viral hepatitis;● osteoporosis;● osteoarthritis;● acute renal failure;● chronic renal failure;● cardiovascular diseases (CVD);● Alzheimer's disease;● Parkinson's disease.
Also, the detection of exosomes concentration and composition as diagnostic markers, the use of exosomes for wound healing and as an adjunct in the treatment for acute pulmonary distress syndrome in COVID-19 are quite promising. But the most common applications of exosomes today are trichology, cosmetology and dermatology.
"Compared to MSC therapy, the risk of immune response, spontaneous cell transformation, necrosis reaction, or even the risk of degeneration into tumor cells is zero with exosomes because exosomes are not cells, they are not living organisms, and do not have the tools to reproduction of themselves."
Inna Gordiienko, biologist of biotechnology laboratory, PhD
Exosomes are, in fact, just a transport for nutrients. In addition, preclinical studies show no toxic effects of exosomes on the liver and kidneys when administered systemically. The absence of an immune response to the introduction of exosomes allows to scale their production from donor stem cells in large quantities. Exosomes can be combined with newly developed biotechnological constructions or methods and are used as carrier-particles. They can be designed for the specific delivery of substances to certain types of cells and tissues.
All these characteristics make exosomes an ideal natural material for the development of nanomedicine. Currently, the research and use of exosomes in medicine gives rise to a new direction in regenerative medicine, which can be called "cell-free therapy" or "next-generation cell therapy".
The number and content of exosomes derived from MSCs is quite dynamic and variable, which is closely related to the state of cell culture, tissue source of cells, cultivation conditions and other factors. Therefore, exosomes derived from MSCs should be studied and used according to certain specifications.
The heterogeneity of MSC exosomes gives them a number of advantages, but there are also some disadvantages. It is important to note that the purification of a certain population of exosomes is still not an easy procedure, to achieve a good level of purification is often difficult.
The information about the size, biochemical structure and description of cell growth or origin conditions is very important.To produce high-quality MSC exosomes, it is necessary to:● unify the production of MSCs and exosomes directly;● regularly test cells with standardized approaches;
Four international societies (SOCRATES, ISEV, ISCT and ISBT) are working to solve these problems. Today, a number of criteria have already been proposed, in particular, it is necessary to determine the number of exosomes obtained from MSCs, their size, to determine the phenotype of exosomes and their biochemical structure. In our next article we will talk about the most promising areas of possible exosomes application and analyze the mechanisms of their work in each case.
Requirements for the production of exosomes for clinical use, we will present in the near future. Follow our news.
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Sources:1. Wei Wumei, Ao Qiang, Wang Xiaohong, Cao Yue, Liu Yanying, Zheng Song Guo, Tian Xiaohong/ Mesenchymal Stem Cell–Derived Exosomes: A Promising Biological Tool in Nanomedicine. Frontiers in Pharmacology (2021)https://www.frontiersin.org/article/10.3389/fphar.2020.590470 2. Nikfarjam, S., Rezaie, J., Zolbanin, N.M. et al. Mesenchymal stem cell derived-exosomes: a modern approach in translational medicine. J Transl Med 18, 449 (2020). https://doi.org/10.1186/s12967-020-02622-33. Mendt, M., Rezvani, K. & Shpall, E. Mesenchymal stem cell-derived exosomes for clinical use. Bone Marrow Transplant 54, 789–792 (2019).https://doi.org/10.1038/s41409-019-0616-z4. Maria Maqsood, Mingzhu Kang, Xiaotao Wu, Jinghua Chen, Liping Teng, Lipeng Qiu. Adult mesenchymal stem cells and their exosomes: Sources, characteristics, and application in regenerative medicine. Life Sciences, Volume 256 (2020)https://doi.org/10.1016/j.lfs.2020.118002