Exosomes are a recently discovered mode of cellular communication. Initially mistaken for scraps, could prove to be a promising tool for diagnosis and therapy. We are used to thinking of our body as a single machine, forgetting that it is instead made up of many parts. Each organ is made up of different tissues and many cells. However, the number of bacteria in our body exceeds that of our cells. And this makes us doubt that we might not be made of dreams but of bacteria. All these parts must communicate with each other to work. Just like in a car.

Cellular communication

Within multicellular systems this communication is of fundamental importance, so that all those processes that regulate the various functions can take place. Cells use different mechanisms to communicate with each other, starting from cell-cell contact thanks to cell junctions; through the release of growth factors, proteins, signal molecules and hormones, to reach even the furthest cells. Another particular mechanism of communication is what occurs at the level of neurons, communicate by nerve transmission. This special communication between nerve cells allows information to be propagated via electrochemical signals.

The exosomes

In the 1980s it was discovered that cells also have particular extra-cellular particles at their disposal, The dry, containing many molecules produced by cells: proteins, DNA and different types of RNA. These are very small vesicles that carry much more information than single signal molecules and are released by different cell types, both in physiological and pathological conditions.

Exosome

How an exosome is made (Photo by Genetics Unzipped)

There is an intense traffic of particles inside and outside the cells, molecules and many other specific signals; this traffic is also present within bodily fluids, where exosomes were also found, managing to communicate in this way even with more distant cells. This communication allows all intra-cellular and extra-cellular activities to take place. It makes complex processes such as metabolism possible, growth, homeostasis and the immune response. Defects in communication between cells, and within the cell itself, lead to imbalances in all these processes which must be strictly regulated. These imbalances can favor the development of cancer or autoimmune diseases.

The release of these lipoprotein vesicles has been observed in animals, in plants and has also been discovered in bacteria. Hypothesizing that they can also amplify or favor the mechanisms used by pathogenic microorganisms. Although it is not an easy task to recognize these particles within the samples, the techniques for separating and identifying them are constantly evolving.

The discovery of exosomes

Exosomes are real cellular messengers. Traded initially as a form of detoxification, used by the cell to eliminate any waste. They were discovered by the researcher Rose Mamelak Johnstone in 1983, while studying the entry of iron into maturing red blood cells. She verified their expulsion from the plasma membrane of mature sheep reticulocytes (red blood cell precursor cells).

Electron microscope photograph of exosomes leaving the reticulocyte, from an article by 1985 by Rose Johnstone and several co-authors. (Rockefeller University Press)

Exosomes are spheroidal or ovoid-shaped structures, of 50-150 nanometers in diameter. They are formed inside the cell and act as a vehicle to transport proteins, lipids and nucleic acids from one cell to another; that is, to transmit messages to other cells. They are surrounded by a membrane with a phospholipid bilayer, in which surface proteins are interposed.

They form from multivesicular bodies, derived from the Golgi apparatus, and in turn fuse with the plasma membrane, from which the exosomes will be expelled. These pass through the body fluids, in fact they are present in the blood, in urine and saliva, in mother's milk, in the amniotic fluid, in semen and cerebrospinal fluid.

Possible uses for diagnosis and therapy

Given their fairly widespread presence within our body, their possible use for diagnostic purposes has been proposed, exploiting exosomes such as biomarker for various diseases. Not only for their involvement in different physiological functions but also for their molecular content, characteristic of the cells from which it derives and which is also well protected by the phospholipid double layer.

Given the enormous potential of these particles, their possible uses in therapy are also investigated. With the aim of counteracting symptoms of neurodegenerative diseases, autoimmune diseases, liver diseases and develop innovative approaches in cancer therapy. For example, taking advantage of these cellular messengers like drug delivery to deliver drugs or therapeutic compounds such as miRNAs, siRNA and chemotherapeutic agents to target cells, so as to improve the effectiveness of the therapy and reduce its toxicity for other cells.

Robert Galasso

SOURCES:

PICTURE CREDITS:

  • https://www.azonano.com/news.aspx?newsID=39360
  • Genetics Unzipped
  • Rockefeller University Press