Exosomes – History and Promise
April 28, 2016 by 2012pharmaceutical
Exosomes – History and Promise
Reporter: Aviva Lev-Ari, PhD, RN
It was discovered some time ago that eukaryotic cells regularly secrete such structures as microvesicles, macromolecular complexes, and small molecules into their ambient environment. Exosomes are one of the types of natural nanoparticles (or nanovesicles) that have shown promise in many areas of research, diagnostics and therapy. They are small lipid membrane vesicles (30-120 nm) generated by fusion of cytoplasmic endosomal multivesicular bodies within the cell surface. Exosomes are found throughout the body in such fluids as blood, saliva, urine, and breast milk. Furthermore, all types of cells secrete them in in vitro culture. It is believed that they have many natural functions, including acting as transporters of nucleic acids (mostly RNA), cytosolic proteins and metabolites to many cells, tissues or organs throughout the body. Much remains to be understood regarding how they are formed, as well as of their targeting and ultimate physiological activity. But many don’t realize that some activities have been rather thoroughly demonstrated─ such as their function in some sort of either local or more systemic intercellular communication.
Exosomes as Tools
General interest in exosomes is now growing for many reasons. One is because of the observation of their natural activity with antigen-presenting cells and in immune responses in the body. Their potential as very powerful biomedical tools of both diagnostic and therapeutic value is now being more widely reported. Applications described include using them as immunotherapeutic reagents, vectors of engineered genetic constructs, and vaccine particles. They’ve also been described as tools in the diagnosis or prognosis of a wide variety of disorders, such as cancer and neurodegenerative diseases. Also, their potential in tissue-level microcommunication is driving interest in such therapeutic activities as cardiac repair following heart attacks. Their potential as biomarkers is being explored because their content has been described as a “fingerprint” of differentiation or signaling or regulation status of the cell generating them. For example, by monitoring the exosomes secreted by transplanted cells, one may be able to predict the status or potentially even the outcome of cell therapy procedures. Clinical trials are in progress for exosomes in many therapeutic functions, for many indications. One example is using dendritic cell-derived exosomes to initiate immune response to cancers.
Exosome product manufacturing involves many distinct areas of study. First of all, we are interested in their efficient and robust generation at a sufficient scale. Also, because they are found in such raw materials as animal serum, avoiding process-related contaminants is a concern. Finally, a variety of means of separating them from other types of extracellular vesicles and cell debris is under study. As exosomes are being examined in so many applications, their production involves many distinct platforms and concerns. First of all, an appropriate and effective culture mode is required for any cell line that is specifically required by the application. Also, one must consider the quality systems and regulatory status of the materials and manufacturing environment for the particular product addressed. Finally, a robust process must be described for the scale and duration of production demanded. As things exist now, their production can be described as
1) the at-scale expansion and culture of the parent cell-line,
2) the collection or harvest of the culture media containing the secreted exosomes, and
3) the isolation or purification of the desired exosomes from not only other macrovesicles, macromolecular complexes, and small molecules, but from such other process contaminants as cellular debris and culture media components.
Sourced through Scoop.it from: msemporda.blogspot.com.es
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