Exosomes are cell mail
For my first science-related post, I want to introduce you to exosomes. Exosomes are small (~30-100 nanometers) spheres that are produced by cells. Many different kinds of cells can produce them, and they can do all kinds of things, including carrying proteins, DNA, or RNA to neighboring or distant cells. Think of them basically as cell mail, carrying important messages between cells. The cargo of the exosome differs depending on what kind of cell the exosome came from, and what kind of cell its target is. For example, exosomes from cancer cells can contain enzymes that break down the surrounding environment and make it easier for cancers to spread. (1) While exosomes from other cell types carry signals that stoke the immune system in response to diseases like sepsis (2).
Now that we have the understanding that cells use exosomes to affect the behavior of other cells, researchers are trying to utilize the exosome system to affect cell behavior. Because exosomes are made by our cells and seem to be tolerated by the body, researchers are working to modify a) the target cells that the exosomes reach, by altering the patterns of proteins on the exosome surface, and b) loading exosomes with cargo that will induce the target cell to act in a way that might help with a particular disease. A good example of this is a study by Zhang, et. al. (3). The authors wanted to find a way to get two anti-inflammatory molecules, curcumin and JSI124 (a Stat3 inhibitor) into the brain, to decrease inflammation in certain brain diseases. The authors found they were able to get exosomes into the brains of mice by placing a droplet containing exosomes into the mouse's nose. These exosomes are taken up by microglia, an important inflammatory cell in the brain. Microglia are brain cells that act as a kind of beneficial scavenger, eating infected cells and coordinating an immune response if they find any problems in the brain's tissues. The authors were also able to show that after treatment with exosomes that contain anti-inflammatory drugs, brain inflammation was reduced. Microglia expressed less interleukin-1beta (IL-1b, a pro-inflammatory molecule), and the severity of the model brain disease, experimental autoimmune encephalitis (EAE) in the mice was reduced. Exosomes that contained an inhibitor of Stat3, reduced the growth of brain tumors in mice as well.
Exosomes could also be manipulated to deliver beneficial drugs to specific target cells in a variety of other diseases. Imagine, for example, if exosomes could be manipulated to target cells of the intestine to calm inflammation of the gut in inflammatory bowel disease (IBD). Or, if chemotherapy drugs could be delivered directly to the tumor using exosomes. This kind of targeting of problem cells might mean that you could decrease the dose of chemotherapy drugs in the patient's system, possibly diminishing the side effects of chemotherapy, such as nausea and hair loss. We're just beginning to understand more about exosomes and the possibilities they may offer. Please ask me questions if you want to know more!
For further reading, please see:
1. http://clincancerres.aacrjournals.org/content/11/7/2492.long
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992732/#B47
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188748/
4. Review on MSC-derived exosomes: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749272/
5. http://www.exocarta.org/
6. http://student4.postech.ac.kr/evpedia2_xe/xe/
7. http://www.asemv.org/
Now that we have the understanding that cells use exosomes to affect the behavior of other cells, researchers are trying to utilize the exosome system to affect cell behavior. Because exosomes are made by our cells and seem to be tolerated by the body, researchers are working to modify a) the target cells that the exosomes reach, by altering the patterns of proteins on the exosome surface, and b) loading exosomes with cargo that will induce the target cell to act in a way that might help with a particular disease. A good example of this is a study by Zhang, et. al. (3). The authors wanted to find a way to get two anti-inflammatory molecules, curcumin and JSI124 (a Stat3 inhibitor) into the brain, to decrease inflammation in certain brain diseases. The authors found they were able to get exosomes into the brains of mice by placing a droplet containing exosomes into the mouse's nose. These exosomes are taken up by microglia, an important inflammatory cell in the brain. Microglia are brain cells that act as a kind of beneficial scavenger, eating infected cells and coordinating an immune response if they find any problems in the brain's tissues. The authors were also able to show that after treatment with exosomes that contain anti-inflammatory drugs, brain inflammation was reduced. Microglia expressed less interleukin-1beta (IL-1b, a pro-inflammatory molecule), and the severity of the model brain disease, experimental autoimmune encephalitis (EAE) in the mice was reduced. Exosomes that contained an inhibitor of Stat3, reduced the growth of brain tumors in mice as well.
Exosomes could also be manipulated to deliver beneficial drugs to specific target cells in a variety of other diseases. Imagine, for example, if exosomes could be manipulated to target cells of the intestine to calm inflammation of the gut in inflammatory bowel disease (IBD). Or, if chemotherapy drugs could be delivered directly to the tumor using exosomes. This kind of targeting of problem cells might mean that you could decrease the dose of chemotherapy drugs in the patient's system, possibly diminishing the side effects of chemotherapy, such as nausea and hair loss. We're just beginning to understand more about exosomes and the possibilities they may offer. Please ask me questions if you want to know more!
For further reading, please see:
1. http://clincancerres.aacrjournals.org/content/11/7/2492.long
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992732/#B47
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188748/
4. Review on MSC-derived exosomes: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749272/
5. http://www.exocarta.org/
6. http://student4.postech.ac.kr/evpedia2_xe/xe/
7. http://www.asemv.org/
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