Exosomes, small spherical shaped vesicles (50 to 150nm in size) are secreted by
almost all types of cells in the body, and thus, are found in the body fluids.
Currently, studies on exosomes form a hot topic of research in the field of
Around 30 years ago, in 1980’s, a scientist named C.V. Harding, then MD / Ph.D.
student, focused on the study of pathways of receptor-mediated endocytosis for
his Ph.D. thesis. In the study, he used rat reticulocytes or maturing blood
cells as his model system because these cells were known to be abundant with
transferrin receptors. During the maturation process, the reticulocytes lose the
transferrin receptor. To visualize this, he incubated reticulocytes with
gold-conjugated transferrin (AuTf) and observed that these AuTf particles are
easily internalized by the reticulocytes. These internalized AuTf particles were
located in many small vesicles present in the multi-vesicular bodies, thus, he
chose to call them as multi-vesicular endosomes (MVE). After performing electron
microscopy, he noticed that these MVE containing tranferrin receptors conjugated
with AuTf particles fuse with plasma membrane and are discarded outside the
cell. These observations revealed a novel mechanism for the loss of transferrin
receptors during maturation of reticulocytes.
Previous to this discovery, these vesicles were thought to be garbage bags of the
cells and were considered to be used by the cells to discard the unwanted
material. Later in 1996, Raposo discovered that immune cells such as B
lymphocytes also secreted exosomes, and they carried membrane-bound molecules
essential for the adaptive immune response. Two years later, further research
demonstrated that the dendritic cells also secrete exosomes and these exosomes
carry functional immune agents that could promote induction of antitumor
responses in mice. These results formed the basis for the hypothesis that
exosomes could play active roles in intercellular communication, and thus, their
potency in clinical applications.
Later in 2007, a group led by Jan Lötvall in Sweden discovered that exosomes
harbor mRNAs and microRNAs. In vitro experiments also suggested that these mRNAs
could be translated into proteins in the target cells, providing the first
demonstration of genetic information transfer via exosomes, thus confirming
their role in intercellular communication. This study triggered the exosome
research around the world and different groups came up with the proof of
exosomes being exploited by normal as well as tumor cells as messengers.
The current challenges in the exosomes field are mainly the technical
difficulties in isolating pure population of exosomes and also getting better
yield of exosomes due of which the data generated are not homogenous across
globe. Also the signaling pathways responsible for the intercellular
communication are still unexplored. Identification of various macromolecules
present in the exosomes and the signaling pathways activated by them in the
recipient cells will give basic understanding about the mechanism underlying
this paracrine functioning of the cells.