Exosome Explosion
These small membrane vesicles do much more than clean up a cell’s trash—they also carry signals to distant parts of the body, where they can impact multiple dimensions of cellular life.
By Clotilde Théry | July 1, 2011
Keith Kasnot
Secreted vesicles known as exosomes were first discovered nearly 30 years ago. But, considered little more than garbage cans whose job was to discard unwanted cellular components, these small vesicles remained little studied for the next decade. Over the past few years, however, evidence has begun to accumulate that these dumpsters also act as messengers, actually conveying information to distant tissues. Exosomes contain cell-specific payloads of proteins, lipids, and genetic material that are transported to other cells, where they alter function and physiology.
Two years ago, I began receiving daily e-mails requesting reprints of my articles on exosomes, details on experimental protocols, and advice on the purification and characterization of the vesicles. Having studied exosomes for more than 10 years, I thought I knew all the other researchers working on the subject, but the requests were from groups I hadn’t heard from before. The flood of inquiries made me realize that the field had been growing, attracting the attention of more and more researchers over a relatively short period of time.
A quick glance at the literature confirmed the trend: while only about 20 PubMed-referenced papers containing the word “exosomes” were published in 2003, and just over 60 in 2007, nearly 500 exosome studies have been published since. To take advantage of this flood of research I organized an international workshop on the subject together with Graça Raposo, who in 1996 discovered exosomes made by immune antigen-presenting cells. A 2005 meeting organized by the late Rose Johnstone, who participated in the first description of exosomes in the 1980s, had drawn 25 scientists to Montreal, Canada; the new meeting, which took place this January at our home institution, the Curie Institute in Paris, attracted nearly 10 times as many attendees. At the meeting, researchers in fields ranging from immunology to neurology and tumor biology presented their recent findings on exosomes and other types of secreted membrane vesicles, including the ability of pathogens to manipulate host exosome activity and the influence of the vesicles on allergies. We also discussed potential clinical applications, such as their use as biomarkers or therapeutic tools.
Exosomes: a history
Exosomes are small in size (around 150 nm in diameter or smaller) and are secreted by most cell types. They are formed inside the cell in compartments known as multivesicular endosomes (MVE), which take up bits of the cytoplasm and its contents into membrane-bound vesicles. MVE were originally thought to merely help traffic extracellular molecules to lysosomes, where they are degraded. But about 25 years ago, researchers described the opposite process—MVE in developing red blood cells fused with the plasma membrane and released their contents, including numerous small vesicles (later dubbed exosomes), outside the cell.
Keith Kasnot
To document this process, researchers cultured immature red blood cells, known as reticulocytes, with radioactive transferrin, or with a radioactive antibody that bound to the surface receptor for transferrin. Every 15 minutes, they fixed subsets of the cells and imaged them using electron microscopy, to follow the transferrin or the receptor as it made its way from the cell surface into the cell via the endocytic pathway, and traveled through different cellular compartments to MVE. The transferrin, still bound to its receptor, was sequestered in small vesicles that formed inside the larger MVE. Surprisingly, the micrographs showed that some of these MVE fused with the plasma membrane and released these small vesicles bearing transferrin and its receptor to the outside of the cell.
But over the next 15 years, exosomes were all but forgotten—until 1996, when Raposo published her discovery that immune cells such as B lymphocytes also secreted exosomes, and that these vesicles carried membrane-bound molecules essential for the adaptive immune response.1 Two years later, further research demonstrated yet another exosome-secreting cell type: the dendritic cell, whose exosomes carried functional immune agents that could promote induction of antitumor responses in mice.2 These results laid the foundation for the hypothesis that exosomes could play active roles in intercellular communication, and prompted explorations into their clinical application. They are being tested as a new type of adjuvant therapy for the treatment of nonoperable lung cancer, currently in a Phase II trial led by the Gustave Roussy Institute in France.3 (Disclosure: The Curie Institute is contributing to the analyses of immune responses.)
...
Read more here/Leia mais aqui: The Scientist
