What are Exosomes?

Exosomes are nano-sized extracellular vesicles ranging between 30-150 nm in diameter that are released by cells during cell-cell communication. They are naturally released by most cell types including stem cells. Exosomes play a key role in intercellular signaling by transferring molecular contents such as proteins, lipids, messenger RNA (mRNA), microRNA (miRNA), and DNA between cells. Their lipid bilayer structure protects the contents during transportation from one cell to another.

Role of Exosomes in Diseases

Researchers have found that exosomes play an important role in various diseases due to their ability to transfer biomolecules between cells. They can aid in disease progression by carrying pathological agents such as proteins and miRNAs between cells. Alternatively, exosomes may be involved in active tissue repair in response to injury or disease. Researchers are studying exosomes to better understand disease development, progression, and therapeutic opportunities. Some roles exosomes play in diseases include:

Cancer Progression and Metastasis

Tumor exosomes have been found to reprogram neighboring and distant cells to support tumor growth, survival, angiogenesis, metastasis, and chemotherapy resistance. They carry oncogenic proteins and miRNAs that alter gene expression in recipient cells. Understanding how cancer-derived exosomes mediate metastasis could lead to new anti-metastatic therapies.

Neurodegenerative diseases

Exosomes from brain cells and astrocytes are involved in intercellular communication in the central nervous system. Changes in their cargo associated with neurodegenerative diseases like Alzheimer's, Parkinson's, and prion diseases may contribute to disease progression. Analyzing their contents could provide disease biomarkers.

Inflammatory Diseases

Immune cell-derived exosomes modulate inflammatory responses by transporting inflammatory mediators between cells. They may promote chronic inflammation in arthritis, inflammatory bowel disease, and atherosclerosis. Controlling exosome secretion and targeting their contents could reduce inflammation.

Viral Exosomes Diagnostic and Therapeutic

Many viruses manipulate exosome biogenesis and secretion pathways to facilitate viral replication, dissemination, and host immune evasion. Exosomes derived during infection transport antigens that prime immune cells for antiviral responses. Understanding how viruses hijack exosomes may lead to new antiviral approaches.

Exosome Biomarkers for Disease Detection and Prognosis

Because exosomes carry molecular signatures from their parent cells, analysis of their cargo provides a minimally invasive "liquid biopsy" approach for disease detection and monitoring. Exosome biomarkers have potential applications in:

Cancer Diagnostics

Certain exosomal proteins and nucleic acids show promise as cancer detection biomarkers. For example, exosomal miRNA profiles can detect early-stage cancers of the gastrointestinal tract, ovaries, and breast with high accuracy. Exosome biomarkers may enable non-invasive cancer screening and monitoring of treatment response.

Neurological Disorders

Levels of pathogenic proteins like tau, alpha-synuclein, and prions in exosomes reflect overall disease burden and could serve as biomarkers for Alzheimer's, Parkinson's, and prion diseases respectively. Exosome analysis avoids the need for invasive cerebrospinal fluid collection.

Kidney Diseases

Exosomes contain kidney tissue-specific proteins, mRNAs, and miRNAs indicative of kidney injury or specific kidney diseases. Studies show they can distinguish acute from chronic kidney injury better than current Exosomes diagnostic and therapeutic tests. This allows for early disease detection.

Prenatal Screening

Fetal cells, DNA, and RNA in maternal blood provide a non-invasive window into the developing fetus. Exosomes derived from placental and fetal cells further improve detection of fetal genetic abnormalities, infections, and developmental defects. This enhances prenatal screening capabilities.

Exosomes as Drug Delivery Systems

The natural ability of exosomes to transport biomolecules between cells is being harnessed for therapeutic development. Some advantages of using exosomes as drug delivery vehicles include:

 Targeted drug delivery: Exosomes can be engineered to target specific recipient cells by modifying surface proteins on the exosome membrane. This allows directed delivery of drug cargo.

 Increased drug stability: Encapsulation within the exosome lipid bilayer protects payload from degradation in biological fluids and allows controlled drug release upon uptake by target cells.

 Reduced Immunogenicity: Since exosomes are naturally secreted vesicles, they elicit lower immune responses than synthetic nanoparticles, improving biocompatibility.

Crossing biological barriers: Exosomes derived from MSCs can cross the blood-brain barrier and deliver therapeutic cargo to treat brain diseases. Gut-localized exosomes may deliver orally administered drugs.

Researchers are loading exosomes with anti-cancer drugs, nucleic acids, proteins and evaluating their efficacy and safety. Exosome therapy holds promise for treating currently untreatable cancers and neurological disorders. However, large-scale exosome production under GMP conditions needs to be established before clinical translation.

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