2014/12/23

Exosomes involved in tissue and organ formation

- A study conducted by CIC bioGUNE, in collaboration with Severo Ochoa Molecular Biology Centre, shows that a Hedgehog protein travels through exosomes, which are small vesicles that are released towards the outside of the cell.

- Considered for many years to be mere containers for cell debris, exosomes have suddenly become the focus of scientific activity as important mediators in physiological processes and as disease biomarkers.

(Bilbao, December 2014).- Exosomes are very small vesicles that are secreted towards the outside of almost all cell types in an organism. They were discovered more than three decades ago, but initially it was thought that they were just a kind of container for cell debris.

In recent years it was discovered that they also act as cell messengers that help nearby or distant cells to communicate, and carry key information between different tissue types, and that their physiology can be altered. They are also involved in cancer progression and metastasis development.

Clinical medicine has also become interested recently in exosomes as part of the development of non-invasive biomarkers for various diseases. In this sense, increasingly larger investments are being made in the development of exosome-based diagnostic methods for cancer, neurodegenerative diseases, tuberculosis, HIV, and other diseases.

A study led by researcher Juan Manuel Falcón-Pérez from CIC bioGUNE, and researcher Isabel Guerrero, from the Severo Ochoa Molecular Biology Centre, has shown that a protein called Hedgehog, which regulates tissue development and stem cell division, uses exosomes as a way of travelling between cells.

"This transport through exosomes helps to establish a concentration gradient for the Hedgehog protein andin combination with other molecules generates a 3D map, which is essential for the formation of the tissue types and organs in an organism," says Juan Manuel Falcón-Pérez.

This work clearly shows not only the presence of the protein in these vesicles, but also the fact that the alteration in the formation of exosomes can create defects in tissue signalling, in which the Hedgehog protein is involved.

This finding is relevant because it helps to generate knowledge of the initial stages of the tissue formation process, and clears the way for the study of new therapeutic tools, since exosomes are vesicles that can be modified or manipulated in order to get them to transport the molecules we want.

"A large number of molecules regulate cell proliferation and differentiation. Our study shows that exosomes are involved in these key processes for organisms to form correctly. This gives us a great opportunity to gain more understanding of the process because it includes a player that was not considered until now," the scientist adds.

Falcón-Pérez also explains that the finding "lays the foundations for the development of a possible therapeutic tool that may help to correct defects, because exosomes can be modified or manipulated in order to get them to transport the molecules we want," although he also points out that "it is hard" at the moment to establish a "direct application", and that it is necessary to know more about the interaction with other components involved in the process.

In order to carry out the work, the scientists have used advanced techniques such as electron microscopy, ultracentrifugation, genetic manipulation of organisms to express and inactivate genes, and various biochemical and cell analyses to assess the effects caused by the manipulation.

The study has been published by Nature Communications, and was assisted by other CIC bioGUNE researchers, such as Rosa Barrio, and Marcus Bischoff from the University of Saint Andrews (Scotland).

- About CIC bioGUNE

The Centre for Cooperative Research in Biosciences CIC bioGUNE, with headquarters in the Bizkaia Science and Technology Park, is a biomedical research organisation that conducts innovative research in the interface between structural, molecular and cellbiology, focusing especially on the study of the molecular bases of disease, to be used in the development of new diagnostic methods and advanced therapies.