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

and drug administration (FDA) has yet to approve their use induced pluripotent stem cells (hiPSCs). HiPSCs are
for the treatment or diagnosis of any conditions. As with currently limited in clinical trials due to their intrinsic
any investigational new drug, extensive clinical studies risk of tumorigenicity. Being undifferentiated cells, they
must be conducted to determine the safety and efficacy of possess a high tumorigenic potential and have been
exosomes. There is no substantial evidence to suggest that linked to the formation of tumors and ectopic tissue,
exosomes directly alter the DNA composition of recipient chromosomal abnormalities, and mutations in cancer-
cells, and they are, therefore, generally considered related genes. 68-71 However, while exosomes derived
safe. 58,59 Multiple studies evaluating the adverse effects of from hiPSCs still offer the benefits of pluripotency,
exosome therapy report no harmful effects at the local, they are not associated with tumorigenicity; while
systemic, and organ levels. 60,61 Local site reactions, such exosomes may affect cell behavior, they do not alter
as redness, swelling, and congestion, were not observed the base DNA sequence in cells. Furthermore, other
in tissue subjugated to exosomal injection. 62-64 Other additional side effects associated with the use of stem
studies have evaluated the cytotoxic effect of exosomes cells, such as infusion toxicity, cellular rejection, and
in vitro and found no adverse effects on hemolysis, cell microvasculature trapping affecting distribution, are not
membranes, DNA, or cell proliferation. Furthermore, observed with exosome use. The inherent characteristics
60
studies have not shown a correlation between exosomes of exosomes include their inability to form tumors,
and organ damage, as assessed through various methods, their smaller nanometer particle size, and their reduced
such as measuring liver and renal function markers, probability of eliciting an immune response from the
as well as pathological examination of abnormalities host. 71-74 The latter property stems from the feature of
or collections of inflammatory cell infiltrates in tissue exosomes being hypo-immunogenic as they are cell-free,
sections of the body, including the heart, liver, lungs, have low expression of MHC-I, and show no expression
kidney, and brain. Another investigation assessing the of MHC-II. 75-77
toxicological characteristics of ADSC-Exos determined
that these exosomes are safe for topical application. They 3.2. Comparative safety profiles
exhibited no indications of oral toxicity, had minimal 3.2.1. Evaluation of evidence for exosomes derived
impact on skin sensation, and caused no irritation to the from human, plant, and animal cells
skin or eyes. 65
Based on existing literature, exosomes are generally
It is imperative to comprehend potential safety concerns categorized into two groups: Those derived from animals
to ensure that patients and providers are well-informed and those from plants. However, among animal-derived
and equipped to address potential complications. While exosomes, the majority originate from human sources,
the majority of preclinical studies suggest that exosomes including both allogenic and autologous exosomes,
may represent a safe avenue for alternative treatment, such as those derived from stem cells and bone marrow,
it is important to recognize the current absence of rather than from other species, which are referred to as
standardized regulations. This lack of regulation can xenogeneic exosomes. 78-80 While current studies are being
jeopardize patient safety, particularly due to the ethical conducted, including on exosomes derived from snakes
dilemmas associated with the sourcing of parent cells and pigs, this section mainly discusses the safety profiles of
used to derive exosomes. In addition, the cultivation of plant-derived exosomes and human-derived exosomes, as
exosomes must adhere to proper sterile protocols. Reports current research is limited regarding other species.
have emerged regarding the utilization of unapproved
exosomes derived from stem cell, placental, and umbilical The safety and quality of exosomes greatly depend on the
cord blood products. Instances have been documented source cell type and the process by which they are obtained.
where individuals who received exosomes derived from Exosomes are cultivated through a multistep process that
C-section placentas contracted infections, prompting the begins with the culturing of the source cells, either cell lines
FDA to issue warnings regarding the use of unapproved or tissue isolates, in a conditioned culture media. Isolation
stem cell-derived products. 66,67 of exosomes can be achieved through a variety of different
processes to separate the extracellular particles from
3.1.2. The risk of cancer and other adverse reactions other components, including ultracentrifugation, density
Currently, cell therapy is limited, and ongoing studies gradient centrifugation, ultrafiltration, precipitation, or
are being conducted to enhance the understanding of affinity-based isolation techniques. 81,82 Further purification
the associated risks, including tumorigenicity. In the occurs to remove any contaminants. These isolated
context of exosome therapy, it is important to discuss the exosomes are then characterized and monitored through
risk of cancer, as exosomes can be derived from human a variety of quantitative and qualitative tests to analyze

Volume 3 Issue 2 (2024) 8 doi: 10.36922/gpd.3230