Tumor cells actively produce, release, and utilize exosomes to promote tumor growth. Mechanisms through which tumor-derived exosomes subserve the tumor are under intense investigation. These exosomes ...are information carriers, conveying molecular and genetic messages from tumor cells to normal or other abnormal cells residing at close or distant sites. Tumor-derived exosomes are found in all body fluids. Upon contact with target cells, they alter phenotypic and functional attributes of recipients, reprogramming them into active contributors to angiogenesis, thrombosis, metastasis, and immunosuppression. Exosomes produced by tumors carry cargos that in part mimic contents of parent cells and are of potential interest as noninvasive biomarkers of cancer. Their role in inhibiting the host antitumor responses and in mediating drug resistance is important for cancer therapy. Tumor-derived exosomes may interfere with cancer immunotherapy, but they also could serve as adjuvants and antigenic components of antitumor vaccines. Their biological roles in cancer development or progression as well as cancer therapy suggest that tumor-derived exosomes are critical components of oncogenic transformation.
Summary
Exosomes are a type of extracellular vesicle (EV) with diameters of 30–150 nm secreted by most of the cells into the extracellular spaces and can alter the microenvironment through ...cell‐to‐cell interactions by fusion with the plasma membrane and subsequent endocytosis and release of the cargo. Because of their biocompatibility, low toxicity and immunogenicity, permeability (even through the blood–brain barrier (BBB)), stability in biological fluids, and ability to accumulate in the lesions with higher specificity, investigators have started making designer's exosomes or engineered exosomes to carry biologically active protein on the surface or inside the exosomes as well as using exosomes to carry drugs, micro RNA, and other products to the site of interest. In this review, we have discussed biogenesis, markers, and contents of various exosomes including exosomes of immune cells. We have also discussed the current methods of making engineered and designer's exosomes as well as the use of engineered exosomes targeting different immune cells in the tumors, stroke, as well as at peripheral blood. Genetic engineering and customizing exosomes create an unlimited opportunity to use in diagnosis and treatment. Very little use has been discovered, and we are far away to reach its limits.
Cell communication through extracellular vesicles (EVs) has been defined for many years and it is not limited only to neighboring cells, but also distant ones in organisms receive these signals. ...These vesicles are secreted from the variety of cells and are composed of a distinctive component such as proteins, lipids, and nucleic acids. EVs have different classified subgroups regarding their cell origin, in this context, exosomes are the most appealing particles in cell biology, especially clinical in recent years and are represented as novel therapeutic agents with numerous advantages alongside and/or over cell therapy. However, cell therapy had a hopeful outcome in gastrointestinal diseases which have minimal alternatives in their treatments. Inflammatory bowel disease (IBD), liver fibrosis, gastrointestinal cancers are the examples that cell therapy and immunotherapy were applied in their treatment, therefore, the cell products like exosomes are the beneficial option in their treatment even cancers with promising results in animal models. In this review, we consider the main defined biogenesis, function, and component of secreted exosomes in different cells with a specific focus on the potential application of these exosomes as a cell‐free therapeutic approach in gastrointestinal diseases like IBD, gastric cancer, and colon cancer. Additionally, exosomes role as therapeutic reagents mainly mesenchymal stem cells and dendritic cell‐derived exosomes in different studies have been under intense investigation and even they are being studied in different clinical trials. Therefore, all these striking functions described for secretome implies the importance of these biocarriers.
In this review, we consider the main defined biogenesis, function and component of secreted exosomes in different cells with a specific focus on the potential application of these exosomes as a cell‐free therapeutic approach in gastrointestinal diseases.
Exosomes: new molecular targets of diseases Samanta, Saheli; Rajasingh, Sheeja; Drosos, Nicholas ...
Acta pharmacologica Sinica,
04/2018, Volume:
39, Issue:
4
Journal Article
Peer reviewed
Open access
Extracellular vesicles (EVs) comprise apoptotic bodies, microvesicles and exosomes, and they perform as key regulators in cell-to-cell communication in normal as well as diseased states. EVs contain ...natural cargo molecules, such as miRNA, mRNA and proteins, and transfer these functional cargos to neighboring cells or more distant cells through circulation. These functionally active molecules then affect distinct signaling cascades. The message conveyed to the recipient cells is dependent upon the composition of the EV, which is determined by the parent cell and the EV biogenesis. Because of their properties such as increased stability in circulation, biocompatibility, low immunogenicity and toxicity, EVs have drawn attention as attractive delivery systems for therapeutics. This review focuses on the functional use of exosomes in therapy and the potential advantages and challenges in using exosomes for therapeutic purposes.
Summary
Recent emergence of exosomes as information carriers between cells has introduced us to a new previously unknown biological communication system. Multi‐directional cross‐talk mediated by ...exosomes carrying proteins, lipids and nucleic acids between normal cells, cells harbouring a pathogen or cancer and immune cells has been instrumental in determining outcomes of physiological as well as pathological conditions. Exosomes play a key role in the broad spectrum of human diseases. In cancer, tumour‐derived exosomes carry multiple immunoinhibitory signals, disable anti‐tumour immune effector cells and promote tumour escape from immune control. Exosomes delivering negative signals to immune cells in cancer, viral infections, autoimmune or other diseases may interfere with therapy and influence outcome. Exosomes can activate tissue cells to produce inhibitory factors and thus can suppress the host immune responses indirectly. Exosomes also promise to be non‐invasive disease biomarkers with a dual capability to provide insights into immune dysfunction as well as disease progression and outcome.
Exosomes are rapidly emerging as an intercellular communication system that plays a key role in human diseases. In cancer, tumor‐derived exosomes carry multiple immunoinhibitory signals, disable anti‐tumor immune effector cells and promote tumor escape from immune control. Exosomes can deliver suppressive signals directly to immune cells or activate tissue cells to produce inhibitory factors and thus can indirectly suppress the host immune responses. Exosomes also promise to serve as non‐invasive disease biomarkers of prognosis and outcome.
Prostate cancer remains a life-threatening disease among men worldwide. The majority of PCa-related mortality results from metastatic disease that is characterized by metastasis of prostate tumor ...cells to various distant organs, such as lung, liver, and bone. Bone metastasis is most common in prostate cancer with osteoblastic and osteolytic lesions. The precise mechanisms underlying PCa metastasis are still being delineated. Intercellular communication is a key feature underlying prostate cancer progression and metastasis. There exists local signaling between prostate cancer cells and cells within the primary tumor microenvironment (TME), in addition to long range signaling wherein tumor cells communicate with sites of future metastases to promote the formation of pre-metastatic niches (PMN) to augment the growth of disseminated tumor cells upon metastasis. Over the last decade, exosomes/ extracellular vesicles have been demonstrated to be involved in such signaling. Exosomes are nanosized extracellular vesicles (EVs), between 30 and 150 nm in thickness, that originate and are released from cells after multivesicular bodies (MVB) fuse with the plasma membrane. These vesicles consist of lipid bilayer membrane enclosing a cargo of biomolecules, including proteins, lipids, RNA, and DNA. Exosomes mediate intercellular communication by transferring their cargo to recipient cells to modulate target cellular functions. In this review, we discuss the contribution of exosomes/extracellular vesicles in prostate cancer progression, in pre-metastatic niche establishment, and in organ-specific metastases. In addition, we briefly discuss the clinical significance of exosomes as biomarkers and therapeutic agents.
Macrophages (Mφs) are characterized by remarkable plasticity, an essential component of chronic inflammation. Thus, an appropriate and timely transition from proinflammatory (M1) to anti‐inflammatory ...(M2) Mφs during wound healing is vital to promoting resolution of acute inflammation and enhancing tissue repair. Herein, exosomes derived from M2‐Mφs (M2‐Exos), which contain putative key regulators driving Mφ polarization, are used as local microenvironmental cues to induce reprogramming of M1‐Mφs toward M2‐Mφs for effective wound management. As an injectable controlled release depot for exosomes, hydrolytically degradable poly(ethylene glycol) (PEG) hydrogels (Exogels) are designed and employed for encapsulating M2‐Exos to maximize their therapeutic effects in cutaneous wound healing. The degradation time of the hydrogels is adjustable from 6 days or up to 27 days by controlling the crosslinking density and tightness. The localization of M2‐Exos leads to a successful local transition from M1‐Mφs to M2‐Mφs within the lesion for more than 6 days, followed by enhanced therapeutic effects including rapid wound closure and increased healing quality in an animal model for cutaneous wound healing. Collectively, the hydrolytically degradable PEG hydrogel‐based exosome delivery system may serve as a potential tool in regulating local polarization state of Mφs, which is crucial for tissue homeostasis and wound repair.
An exosome‐encapsulated hydrogel system to reprogramming M1 into M2 Mφs is designed for maximizing their therapeutic effects in cutaneous wound healing. By controlling the crosslinking density and tightness, the degradation time of the hydrogel can be adjusted, and the localization and sustained release of exosomes leads to rapid wound closure and improvement of healing quality.
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