The discovery and research on exosomes has raised hopes for treating different pathologies in regenerative medicine. It has been demonstrated in new studies that exosomes show a great opportunity on cell therapy, and it has been reported as well that Mesenchymal stem cells (MSCs) can potentially deal with various degenerative diseases thanks to their extracellular vesicle (EV), and more specifically to the exosomes specific paracrine effects.
In this sense, the application of exosomes can overcome several disadvantages associated with therapies using whole cells. Because of their adequate size and stability, exosomes are being promoted as therapeutic agents that transfer signal factors to recipient cells.
Among the various types of stem cells, MSCs present substantial transdifferentiation properties after transplantation into target sites. Due to their collection simplicity and their presence in most tissues, MSCs are by far the most widely used cells in regenerative medicine compared to other types of stem cells.
Unfortunately, obtaining cells with similar and typical characteristics is not completely controllable. Viability of transplanted cells, migration to injured sites and integration with host cells are the main obstacles affecting the efficacy of cell therapies.
Moreover, a large number of exogenously administered MSCs are eliminated independently of immune system reaction due to mechanical stress and lack of supporting niche. In correlation, these disadvantages have led researchers to target in exosomes as a promising area of stem cell-based therapies..
Compared to their stem cells, MSC-Exosomes are more stable and can reduce the security risks associated with the delivery of viable cells, such as the risk of occlusion in the microvasculature. MSC-Exosomes can be used to develop cell-free exosome-based therapies for regenerative medicine and may provide an alternative to MSC-based therapy.
Through the combination of nanotechnology and biotechnology, exosomes have arisen as breakthrough tools for the development of nanomedicine. So, stem cells, especially MSCs, can release signaling molecules into exosomes to remotely regulate the behavior of recipient cells. These exosomes are found in biofluids and contain a variety of signaling molecules, such as miRNA, mRNA, lipids, DNA and proteins.
This is the reason why these nanoscale biological vesicles, EVs, in particular, mesenchymal stem cell-derived exosomes (MSC-exosomes), have been explored in the diagnosis, prevention and treatment of many diseases.
Here we describe some of the main advantages that exosomes have demonstrated so far in their use in regenerative medicine:
► Exosomes are the mediators of stem cell paracrine action. They participate in the transmission of information between cells and are considered to be the main mechanism of disease treatment.
► Exosomes can work as biological carriers containing specific ingredients, or can be combined with existing or newly developed compositions.
► They can be engineered to target specific cells or tissues, plus exosomes have autonomous targeting capabilities and can be targeted to the lesion tissue, which is conducive to making them drug delivery systems.
Therefore, all these characteristics make exosomes the ideal natural resource for the development of nanomedicine, which, compared to cell therapy, is safer and is the best alternative to current cell-free therapy..
Fast development of nanomedicine and biotechnology integration allows the use of , exosomes in new applications.
Currently, the main driving areas in the study of exosomes are focused on three directions: the mediation of cellular behavior through intercellular communication, biomarker screening, and drug carrier research and development.
Therefore, due to the intended functions of exosomes, they can be further applied in the fields of medicine and health.
Some studies report that proteomics and biophysical techniques can be used to quantify exosome -related proteins at the molecular level, thus furthering the research process of exosome engineering.
Scientifics all over the world have been working in order to use exosomes as diagnostic biomarkers. As a result of all those investigations nowadays deeper analysis of the exosome features isolated from different body fluids is a rising field
As we mentioned before, exosomes can be used as drug delivery carriers for cell-targeting therapy and they have being also studied as new therapy cell targets.
Moreover, recent studies have shown that exosomes play a significant role in tumors, autoimmune disease and many other diseases, which can be a key direction to apply these extracellular vesicles on regenerative medicine.
However, the most scientifically studied cells in regenerative medicine are MSCs, because as we have addressed before, they play a significant role in tissue regeneration and repair and generate local anti-inflammatory and healing signals.
In this sense, studies have shown that EVs derived from MSCs, particularly exosomes, can play an obvious therapeutic role in diseases of tissue damage or inflammation, and they have great potential In the future.
Despite the advantaged we have been mentioned, technologies associated with exosome isolation and purification have been particularly challenging for the research community. Until now, most of the isolation and purification tools have not get to overcome problems related to the heterogeneity in exosome size and cargo.
These are some of the main disadvantages we can find in the application of exosomes in regenerative medicine:
► Lack of standard isolation and purification protocols: Until now, different isolation methods such as precipitation, ultracentrifugation, ultrafiltration, size separation, microfluidic isolation and antibody affinity capture have been developed for Exosome isolation from biological fluids. Noteworthy, these techniques are laborious, time-consuming and expensive without established protocols.
► Risk of infectious agent transmission: Isolation of Exosomes via the high-speed pelleting method can lead to mechanical damage, exosomal membrane distortion, protein aggregation, lipoprotein contamination and low-rate purity. Furthermore, low-yield rate and alteration of exosomal cargo are possible in Exosome collection via ultracentrifugation.
► Effect of storage conditions on exosome function and profile composition: Storage is another critical issue related to Exosome application in regenerative medicine. It is suggested that the lack of storage protocols can affect their size and composition.
► Batch-to-Batch inconsistencies: The type of guidelines, methods and supplements used for parent MSC cultivation and donor-specific factors affect exosome profile and batch-to-batch variability, also lack of standards to use as a control
► It has been confirmed that the exosomal cargo is directly altered when the host cells are exposed to stressful conditions, leading to the increase of distinct factors and proinflammatory cytokines inside Exosomes. Moreover, molecular identification of isolated Exosomes has indicated a close correlation between cargo type and levels with passage number.
To overcome these disadvantages, at Immunostep we work in order to offer solutions to all these challenges and that is why we have worked non-stop and build a exosome products and tools catalog that covers some of the issues mentioned before: discover all the kits, standards and tools and protocols we have available for the highly sensitive, safe and reproducible isolation, detection and characterization of exosomes.
Since MSC exosomes have many advantages, there is no doubt that they will make great progress in the medical field in the future. Further efforts should be dedicated to basic research on MSC exosomes, such as further exploring their processing mechanism, efficient extraction and separation methods, and standardized production.
At the same time, it is critical that clinical research is also actively conducted with comprehensive consideration of various factors related to the safety of the patients.
Furthermore, as a branch of liquid biopsy, exosomes have brought new imagination to the diagnostic market which makes urgent to explore the concrete mechanism and make exosomes to be a practical treatment tool in clinical medicine.
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