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Gene & Protein in Disease                                          A review of exosome-mediated treatments



            and confirm the morphology, concentration, and surface   more favorable when derived from plants.  Plant-derived
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            markers of the exosomes.  Finally, exosome products are   exosomes are also proposed to carry a lower risk of eliciting
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            stored at −80°C to maintain their stability and biological   an immune response and exhibit greater biocompatibility
            activity.  The process of obtaining plant-derived exosomes   as they originate from a non-animal source. 92,108  Given the
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            is more limited and is based on the standard techniques   natural incorporation of agricultural products into the
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            described above for animal-derived exosomes.  However,   human diet, plant-derived exosomes may offer enhanced
            modified techniques and additional considerations are   compatibility. In contrast, animal-derived exosomes bear
            required, as both types of cells have a different chemical   closer  resemblance to  human proteins, which  increases
            composition while sharing a similar structure. Certain   their risk for rejection.
            techniques that have been successfully applied in animal-  Addressing the risk of allogeneic reactions is crucial
            derived cells do not work for plant-derived cells, such as   when considering the application of various exosome
            immunoaffinity capture, as there is a limitation in labeling   types. Allogeneic reactions occur when the recipient’s
            plant proteins and identifying common plant antibodies,
            which are important in the characterization phase of   immune system identifies transplanted tissues or cells
                                                               from a donor as foreign, eliciting an immune response
            cultivation. There is also a need for additional steps, such as   against them. Currently, the literature showcases mixed
            multiple rounds of centrifugation to separate contaminates   results on the immunogenicity of exosomes. Although
            and certain plant components, such as cellulose and
            starch. 85,86                                      limited, some laboratory and clinical studies indicate
                                                               that exosomes derived from allogeneic stem cells have
              In summary, the process of obtaining exosomes involves   demonstrated  a favorable  safety profile  with minimal
            careful isolation, purification, and characterization to   immediate and delayed adverse effects. For instance, their
            ensure the quality and integrity of preparation, which   use in mitigating inflammation in COVID-19  patients
            is  crucial to  the  downstream  applications  and  safety  of   has shown promising results. 109,110  Moreover, compared
            exosomes in research and the clinical setting.     to conventional cell therapy, exosome administration

              Overall, both plant-derived and human-derived    has been associated with a lower incidence of immune
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            exosomes exhibit significant promise in terms of efficacy   rejection.  However, as exosomes carry a small amount
            and safety, sharing a similar structure. The safety and   of allogenic protein, which can stimulate an autoimmune
            biocompatibility of plant-derived exosomes have been   response, their exact potential to interact with the body’s
            investigated through in vitro and in vivo models. 87-92  These   immune system still requires better understanding. One
            studies reveal a low risk and minimal systemic drug toxicity   study investigated the induction of antigen-specific naïve
            associated with the use of these exosomes. Notably, there   CD4+ T cell activation  in  vivo through the injection
            were no observed instances of tissue damage, alterations in   of antigen-bearing exosomes and found that antigen-
            immunity, pathological or histological changes in organs,   dependent T cell stimulation occurred only when mature
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            or increases in inflammatory markers or liver enzymes. 93-96    CD8α and dendritic cells present in the cultures.
            Moreover,  the  literature  demonstrates  the  effective   Therefore, it seems many factors are at play when
            application of plant-derived nanovesicles across various   assessing the risk of allogeneic reactions with exosome
            disease  models,  including  inflammation,  tumors,  and   use. From the types of cell surface markers present on
            infections, as well as tissue regeneration, cell proliferation,   the exosome to the potential environment the exosome
            and wound healing. 97-101                          will be interacting with, further emphasizing the
                                                               importance of ensuring the cultivation process has strict
              However, it is essential to note that the use of plant-
            derived  exosomes  is  less  prevalent  and  less  extensively   measures.  Through  the  establishment  of  standardized
                                                               cultivation methods, studies can focus on enhancing the
            researched compared to their human-derived counterparts,
            resulting in limitations in current studies. Nevertheless,   purification process of exosomes to minimize the risk of
                                                               allogeneic reactions. One prevalent approach involves
            the existing literature suggests several advantages of   conducting host cell protein and DNA analyses during
            using plant-derived exosomes over human-derived ones.   the characterization phase. By identifying the presence of
            These advantages include easier mass production, ethical
            sourcing, reduced immunogenicity, and a lower risk of   parent cell components, this method offers insight into
            rejection reactions as allografts. 102-106  Human-derived   how process-related impurities may affect the product’s
            exosomes, sourced from components such as bone     safety  by  potentially  inducing  undesired  immunogenic
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            marrow  and stem  cells,  involve  more  time-consuming,   responses.
            expensive, and limited production processes compared   It is also important to acknowledge the disadvantages
            to sourcing from plants. Consequently, exosome yield is   of plant-derived exosomes, including their challenges


            Volume 3 Issue 2 (2024)                         9                               doi: 10.36922/gpd.3230
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