Exosomes: Native vs Manufactured
Exosomes have, in a short period, become the focus of much attention in regenerative medicine. Of particular interest are exosomes that are derived from mesenchymal stromal cells. So what are exosomes? Exosomes are tiny, membrane-bound extracellular vesicles that have a unique generation pathway and are released from and taken up by most cells.(1) They are often so small that they are difficult to quantify by traditional methods. Therefore, either specialized equipment or ELISA assays are necessary for the quantification of exosome numbers in a product.
The contents of an exosome vary by the type and environment of the particular cell that produces it, but each exosome can typically carry a vast array of proteins, microRNA, mRNA, DNA, lipids, and peptides.(2) With this impressive cargo and its ability to transfer information, the use of exosomes as a potential cellular therapy is significant. However, there are challenges in the production and selection of exosomes.
Large-scale production of exosomes is difficult and can alter certain cell behavior and characteristics.(2) In order to mass-produce exosomes, cells are plated on a tissue culture dish and grown. The cell culture media is removed and exosomes are isolated from the media. Exosomes manufactured in this manner have no specificity, the exosomes are being produced as a result of the environment they are in. The cells that are being grown in the artificial environment are problematic and the exosomes produced due to this artificial environment have the potential of having no therapeutic benefit.(3)
Exosomes from native tissue are more specific in their functionality and purpose
Wharton’s jelly of the umbilical cord and other birth tissues contain naturally produced exosomes. One function of the birth tissues is to provide a suitable environment for the developing fetus and prevent rejection of that fetus by the mother. Exosomes found in these tissues would contain cytokines, mRNA, miRNA, and DNA that would be specific to this function.
Exosomes are not just products of cell cultures but are abundantly present in our bodies. It is important to understand that the molecular mechanism involved in exosome production and distribution has not been fully understood and will take time to decipher.
1. Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles and friends. J. Cell Biol. 200(4), 373–383 (2013).
2. Whitford W, Guterstam P. Exosome manufacturing status. Future Med Chem. 2019 May;11(10):1225-1236. doi: 10.4155/fmc-2018-0417. PMID: 31280675.
3. Brindley D, Moorthy K, Lee JH, Mason C, Kim HW, Wall I. Bioprocess forces and their impact on cell behavior: implications for bone regeneration therapy. J. Tissue Eng. 2011, 620247 (2011).