Cells from various origins release vesicles with unique biophysical and biochemical properties, making them of interest for diagnostic and therapeutic purposes. These extracellular vesicles are classified based on their biogenesis and size: vesicles formed by exocytosis of multivesicular bodies are called exosomes (with diameters from 30 to 200nm), vesicles budded directly from the plasma membrane are called microvesicles (with diameters from 100 to 1000nm) and vesicles derived from apoptotic cells are apoptotic bodies (with diameters from 1μm to 5μm). Extracellular vesicles play an important role in intercellular communication (they transfer proteins and/or miRNA between cells), therefore, they could be used as useful biomarkers of various diseases and drug delivery vehicles. In this review, we highlight fundamental information of extracellular vesicles including vesicle classification, standard protocols for isolation and characterization.

View full abstract

Exosomes are membrane vesicles secreted from cells. Exosomes are endogenous delivery vehicles for biological molecules such as nucleic acids, proteins and lipids. Therefore, the development of exosome-based DDS is expected. The information on the tissue distribution of exosomes is prerequisite for the development of exosome-based DDS. However, sufficient data have not been obtained at present to systematically understand the tissue distribution of exosomes. Here we summarize the characteristics of the tissue distribution of exosomes and introduce our recent results on the subject.

View full abstract

The tumor microenvironment is a complex tissue comprising variable numbers of tumor cells, epithelial cells that originated cancer cells, fibroblasts, endothelial cells, and infiltrating leucocytes.Cell-cell communication of cancer cells and microenvironmental cells are critical for the acquisition of malignancy in human cancer. It has been shown how cytokines can control cancer cell-mediated phenotypic changes in the cellular microenvironment. Cytokines are considered key molecules for controlling autocrine or paracrine communications within and between individual cell types. Although the secretion of humoral factors from cancer cells to microenvironmental cells is essential for metastasis during cancer development, the precise molecular mechanisms of cell-cell communications of cancer cells and microenvironmental cells remain unclear. Recent reports highlight that the small membrane vesicle, exosome, which contains various types of proteins, mRNA, non-coding RNA and miRNAs, is novel player in cell-cell communication. In the last few years, it has become clear that exosome play critical roles in mediating cell-cell communication, specifically among immune cells, endothelial cells, fibroblasts and cancer cells. These findings provide evidences that components in exosome are required for cell-cell communication in various physiological and pathological conditions. In this review, we will introduce recent research on the contribution of components in exosome in cancer metastasis and the application of exosome in diagnosis and therapy against cancer development.

View full abstract

A variety of cells release phospholipid membrane vesicles that are thought to play key roles in cell-cell communication, antigen presentation, and the spread of infectious agents. The membrane vesicles derived from the late endosomes called Exosomes. The various proteins, messenger RNAs (mRNAs) and microRNAs (miRNAs) carried by the exosomes to the cells in remote locations like a message in a bottle. The form to be protected encapsulated miRNA from ribonuclease (RNase) in the body fluid is ideal carrier for nucleic acid drugs. In addition, since the exosomes is constructed by self-component, the antigenicity and toxicity are expected to be low. It's extremely important property in carrier for drug delivery. This review presents an overview of the potential roles of exosomes with respect to carrier for miRNA delivery system.

View full abstract

Secreted membrane vesicles called exosomes play important roles in intercellular communications. Exosomes contain various molecules such as proteins, microRNAs and mRNAs, and mimic, at least in part, the roles that are played by their originating cells. Thus, it is expected that mesenchymal stem cells (MSC)-derived exosomes (MSC-exosomes) can serve as drugs for various types of diseases, because MSCs have attracted much attention as a novel therapeutic source for a wide range of diseases. In this article, we will summarize the latest reports on the therapeutic potential of MSC-exosomes for several types of diseases. We also discuss possible therapeutic strategies using MSC-exosomes, and hurdles to be overcome for realization of MSC-exosome based therapy.

View full abstract

There are a few reports about the role of exosomes released from anti-tumor immune cells including T cells, NK cells, DCs or macrophages. On the other hand, it has been clarified that tumor cell-derived exosomes play a crucial role in the formation of tumor microenvironment and epithelial-mesenchymal transition (EMT) of tumors by cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) under the effect of exosomal microRNAs (miRs) and proteins. In addition, tumor-derived exosomes have been reported to attenuate tumoricidal immune responses. In this review, we describe the possibility of exosome-based tumor immunotherapy followed by understanding biological significances of immune cell- and tumor cell-derived exosomes.

View full abstract

Certolizumab pegol (CZP), a novel biological agent, is a PEGylated Fab' fragment of a humanized anti-human TNFα monoclonal antibody. CZP has shown unique pharmacokinetic and pharmacodynamic profiles compared to conventional anti-TNF agents. These characteristics are thought to be the results of its unique structural features, including monovalence, lack of Fc, and PEGylation. CZP rapidly ameliorated signs and symptoms of rheumatoid arthritis (RA), prevented progression of joint destruction, and improved health-related quality of life in patients with active RA. CZP was approved in Japan for the treatment of RA in December 2012.

View full abstract