An Introduction of Exosomes

Figure 1. The morphology of exosomes.

Biogenesis of exosomes

The specific biogenetic pathway of exosomes begins with the budding of early endosomes, which are the initial vesicles formed from the plasma membrane. During the maturation of these vesicles, certain regions of the endosomes start to invaginate, and gradually move into the endosomal space to form intraluminal vesicles (ILVs). At the same time, cellular materials become enclosed within the ILVs. Eventually, this leads to the formation of multivesicular bodies (MVBs). If an MVB fuses with a lysosome, the contents of the ILVs will be degraded [3, 4]. However, if the MVB fuses with the plasma membrane of the cell, the ILVs will be released outside the cell, and form into exosomes (Figure 2) [3]. Apparently, the whole process depends on the combined function of a variety of cellular components.

Figure 2. Schematic of the exosome machinery.

The process of exosome generation takes several hours to days and is closely dependent on the cell types, the physiological state of the cells, and the influences of external conditions. Different type of cells may vary in the speed and time of exosome production. For example, actively secreting cells, such as immune cells or tumor cells, may produce exosomes more quickly than cells like fibroblasts. Additionally, the activation state of the cells, their proliferation rate, and external stimuli including inflammation, hypoxia and chemical induction can also affect the period of time needed for exosome biogenesis [5].

Components of Exosomes

The molecular components of exosomes can be roughly divided into three categories: proteins, lipids, and nucleic acids. The molecular composition of exosomes is  dynamic and varies significantly based on the cell type from which they are secreted. Proteins enriched in exosomes can be broadly divided into common proteins and cell type-specific proteins. Common proteins contain members of the endosomal sorting complex required for transport machinery (ALIX, TSG101), heat-shock proteins (HSP60, HSP70, and HSP90), and tetraspanins (e.g., CD9, CD26, CD53, CD63, CD81 and CD82) [6, 7].

In addition to common proteins, exosomes also carry cell type-specific proteins that depend on the types and conditions of their parent cells. For example, exosomes from immune cells may be enriched with proteins related to immune responses, while exosomes from neuronal cells may contain neurotrophic factors and other nerve-related proteins [8, 9].

Exosomes are enriched in specific lipids including cholesterol, sphingomyelin, phosphatidylserine, ceramide, glycosphingolipids, and phosphatidylcholine with short saturated fatty acids, which are essential for their structure, function, and role in intercellular communication [6].

Along with proteins and lipids, exosomes also carry a variety of nucleic acid components, including noncoding RNA (miRNA, lncRNA and circRNA), mRNA, and DNA fragments. These nucleic acids play significant roles such as facilitating intercellular communication and influencing recipient cell behavior. Figure 3 shows the schematic structure of an exosome [6].

Figure 3.Structure of an exosome.

Exosomes can functionally transfer their protein, lipid and genetic cargos from parent cells to recipient cells under both physiological and pathological conditions as they diffuse. There are at least two major mechanisms for delivering this information: the direct fusion with plasma membrane or internalisation. Exosomes can fuse with the plasma membrane to release their content directly into the cytosol of recipient cells, Alternatively, exosomes are internalised by recipient cells followed by cargo release. In the latter case, the endocytic pathways are commonly involved. Nevertheless, in either process, both the exosomes themselves and their released contents play crucial roles in cellular communication and influence a broad range of physiological processes such as cell growth and migration, immune responses, central nervous system (CNS) communication, stem cell maintenance, tissue repair, and pathological processes such as in neurodegeneration, cardiovascular diseases, cancer and inflammation [10].

Categories and Functions of Exosomes

Exosomes were first discovered in sheep reticulocytes and are readily accessible in almost all biological fluids such as blood, urine, saliva, cerebrospinal fluid (CSF), semen, bile, gastric acid, and tears. They are secreted by almost all types of cells.

Although the secretion mechanisms of each type of cells are generally similar, the cell type from which exosomes are derived determines their function. Since May 2025, AcceGen starts to provide a comprehensive suite of exosomes under five categories, including Mesenchymal Stem Cell-Derived Exosomes, Cancer Cell Line-Derived Exosomes, Primary Cell-Derived Exosomes, Biofluid-Derived Exosomes and Others. So far, these exosome products cover the species of human, mouse, rat, and bovine.

Mesenchymal Stem Cell-Derived Exosomes

The role of mesenchymal stem cell (MSC)-derived exosomes is gaining increasing attention due to their functions in facilitating cell-to-cell communication, and playing crucial roles in tissue regeneration, immune regulation, inflammation modulation, and drug delivery.

There are some advantages to work with MSC-derived exosomes. To start with, MSC-derived exosomes are less likely to induce immune rejection or tumorigenicity compared to MSCs themselves. They are also easier to be preserved than stem cells. Moreover, MSC-derived exosomes are a promising tool for cell-free therapy with a wide range of potential applications in regenerative medicine, these exosomes can be engineered to target specific cells or tissues, enhancing their potential therapeutic efficacy. Furthermore, studies on therapeutic applications of MSC-derived exosomes in areas like wound healing, cardiovascular disease, neurodegenerative disease, osteoarthritis, graft-versus-host disease, cancer, and type 1 diabetes might all be supported by these exosome products.

Cancer Cell Line-Derived Exosomes

Cancer cells release higher levels of exosomes compared to normal cells. Cancer cell line-derived exosomes is a powerful tool in cancer research. These exosomes play crucial roles in cancer development and progression by facilitating the communication between cancer cells and their microenvironment including other cells like immune cells and stromal cells.

More specifically, exosomes released from cancer cells can promote cell proliferation angiogenesis and invasion, ultimately contributing to tumor progression. Furthermore, they can facilitate metastasis by promoting the formation of metastatic niches, facilitating tumor cells escape and growing in distant organs. Additionally, they also modulate immune system, suppressing anti-tumor immunity and enabling tumor cells to escape immune surveillance. In addition, they are also potential biomarkers for cancer diagnosis and prognosis. Meanwhile, they are also used to deliver molecules that alter the drug-sensitive status of recipient cells and engineered to deliver therapeutic drugs to enhance the effectiveness of cancer treatments. As time goes by, more exosome-based therapeutic strategies are being explored for cancer treatment.

Primary Cell-Derived Exosomes

Primary cell-derived exosomes are secreted by a wide range of primary cell types. These exosomes carry vital information and act as intercellular messengers, enabling cellular communication and influencing biological processes. Exosomes derived from primary cells are essential models for the study of biological roles of exosomes in natural cell-to-cell communication in various physiological and pathological processes such as immune responses, tissue regeneration, and disease progression. In addition, it is worth mentioning that exosomes derived from primary cells are particularly suited for therapeutic potential exploration in areas like gene therapy, regenerative medicine and cancer treatment.

AcceGen provides high-quality primary cell-derived exosomes secreted by various types of primary cells like fibroblasts, epithelial cells, endothelial cells, and muscle cells etc. These exosome products offer a physiologically relevant model to unravel their complex roles in various biological processes, disease pathogenesis and potential for novel therapeutic interventions.

Biofluid-Derived Exosomes

Biofluid-derived exosomes are released by cells in bodily fluids such as blood, CSF and urine. As the content of exosomes derived from biofluid closely reflect the health and status of their parent cells, they have been widely used as potential biomarkers for disease detection and monitoring, as well as therapeutic agents for drug delivery and regenerative medicine.

AcceGen provides high-quality biofluid-derived exosomes generated from various types of biofluid including plasma, serum, saliva, CSF, breast milk, ascites and urine, each offering unique opportunities for different research needs. For example, circulating exosomes in blood carry information of various tissues and organs, making them valuable for detecting diseases. Exosomes derived from urine reflect kidney health and function, and are being investigated as biomarkers for kidney diseases. Exosomes in CSF provide insights into CNS diseases and are being studied for their roles in neurodegenerative disorders. Over all, these exosomes allow researchers to explore the molecular cargo in biofluids, offering insights into early diagnosis, disease mechanisms, and new therapeutic strategies.