Exosomes: biogenesis, biologic function and clinical potential

Exosomes: biogenesis, biologic function and clinical potential

2019 | Yuan Zhang, Yunfeng Liu, Haiying Liu, Wai Ho Tang
Exosomes are small membrane vesicles released by cells, containing proteins, lipids, and nucleic acids. They can be taken up by neighboring or distant cells, delivering bioactive compounds that reprogram recipient cells. Exosomes have significant biological interest due to their potential as non-invasive diagnostic biomarkers and therapeutic nanocarriers. This review discusses recent advances in understanding exosome biogenesis, molecular composition, and technologies used in exosome research. It also explores their potential as diagnostic and therapeutic tools, focusing on their cell-lineage and state-specific contents, and their ability to deliver drugs and genes. Exosome research is still in its early stages, and a deeper understanding of their formation and targeting mechanisms is needed to fully harness their physiological activities. Exosomes are formed from late endosomes, which undergo inward budding to create intraluminal vesicles (ILVs). These ILVs are then released into the extracellular space or trafficked to lysosomes for degradation. The formation of ILVs requires the endosomal sorting complex required for transport (ESCRT) function, which involves several protein complexes working together to facilitate MVB formation, vesicle budding, and protein cargo sorting. Additionally, raft-based microdomains may be involved in sorting exosomal cargo in an ESCRT-independent manner. Exosomes also contain various proteins, such as tetraspanins, which participate in exosome biogenesis and protein loading. They also contain different patterns of RNAs, including microRNAs (miRs), which can be transferred between cells and influence recipient cell phenotypes. Exosomes also contain lipids, which contribute to their stability and structural rigidity. Exosomal lipids may interact with lipid transfer proteins in recipient cells, influencing cellular processes. Exosomes can mediate intercellular communication by delivering bioactive molecules to recipient cells, which can lead to changes in cell behavior and phenotype. Exosomes have important roles in immune regulation, including antigen presentation, immune activation, immune suppression, and immune tolerance. Exosomes derived from CD4⁺ T cells and CD8⁺ T cells can bind to dendritic cells (DCs), leading to DC-mediated T cell silence. Exosomes secreted by regulatory T cells contain microRNAs that can inhibit Th1 immune response and mediate immune suppression. Exosomes derived from B lymphoblasts can induce human and mouse-antigen specific T cell activation. Exosomes derived from DCs can present tumor peptides to naive T lymphocytes and prime specific cytotoxic T lymphocytes. Exosomes have therapeutic potential as drug delivery vehicles due to their ability to target specific cells or tissues. They can be used to deliver genetic material, such as siRNAs, to target cells, leading to gene silencing and therapeutic effects. Exosomes can also be used to deliver proteins, such as catalase, which can have therapeutic effects in diseases like Parkinson's disease. Exosomes derived from dendritic cells (Dex) pulsed with tumor peptides haveExosomes are small membrane vesicles released by cells, containing proteins, lipids, and nucleic acids. They can be taken up by neighboring or distant cells, delivering bioactive compounds that reprogram recipient cells. Exosomes have significant biological interest due to their potential as non-invasive diagnostic biomarkers and therapeutic nanocarriers. This review discusses recent advances in understanding exosome biogenesis, molecular composition, and technologies used in exosome research. It also explores their potential as diagnostic and therapeutic tools, focusing on their cell-lineage and state-specific contents, and their ability to deliver drugs and genes. Exosome research is still in its early stages, and a deeper understanding of their formation and targeting mechanisms is needed to fully harness their physiological activities. Exosomes are formed from late endosomes, which undergo inward budding to create intraluminal vesicles (ILVs). These ILVs are then released into the extracellular space or trafficked to lysosomes for degradation. The formation of ILVs requires the endosomal sorting complex required for transport (ESCRT) function, which involves several protein complexes working together to facilitate MVB formation, vesicle budding, and protein cargo sorting. Additionally, raft-based microdomains may be involved in sorting exosomal cargo in an ESCRT-independent manner. Exosomes also contain various proteins, such as tetraspanins, which participate in exosome biogenesis and protein loading. They also contain different patterns of RNAs, including microRNAs (miRs), which can be transferred between cells and influence recipient cell phenotypes. Exosomes also contain lipids, which contribute to their stability and structural rigidity. Exosomal lipids may interact with lipid transfer proteins in recipient cells, influencing cellular processes. Exosomes can mediate intercellular communication by delivering bioactive molecules to recipient cells, which can lead to changes in cell behavior and phenotype. Exosomes have important roles in immune regulation, including antigen presentation, immune activation, immune suppression, and immune tolerance. Exosomes derived from CD4⁺ T cells and CD8⁺ T cells can bind to dendritic cells (DCs), leading to DC-mediated T cell silence. Exosomes secreted by regulatory T cells contain microRNAs that can inhibit Th1 immune response and mediate immune suppression. Exosomes derived from B lymphoblasts can induce human and mouse-antigen specific T cell activation. Exosomes derived from DCs can present tumor peptides to naive T lymphocytes and prime specific cytotoxic T lymphocytes. Exosomes have therapeutic potential as drug delivery vehicles due to their ability to target specific cells or tissues. They can be used to deliver genetic material, such as siRNAs, to target cells, leading to gene silencing and therapeutic effects. Exosomes can also be used to deliver proteins, such as catalase, which can have therapeutic effects in diseases like Parkinson's disease. Exosomes derived from dendritic cells (Dex) pulsed with tumor peptides have
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