Damian Sendler: Cells’ ability to communicate with each other is critical to the functioning of the body as a whole. The nervous system and the production of hormones have long been recognized as two methods of cell-to-cell communication. Exosomes—tiny sacs or vesicles containing protein and RNA molecules that cells discharge into the circulation where they can be picked up by other cells to regulate metabolism—have emerged as an important third mode of communication in the last five years. 

Damian Jacob Sendler: In many laboratories, microRNAs are carried via exosomes. It is possible for these RNAs to influence the ability of longer RNAs to create diverse proteins and control cell activity. Many elements of cell behavior are affected by microRNAs in health and sickness. 

Damian Sendler

C. Ronald Kahn, MD, a senior investigator at Joslin Diabetes Center and professor of medicine at Harvard Medical School, has revealed how cells select a group of microRNAs for their exosomes. 

Kahn, who is the corresponding author on a Nature paper outlining the findings, stated, “Our work offers a major insight into this new mechanism of cellular communication, because it breaks the code of why cells secrete some microRNAs and why they retain others,” 

Kahn and his colleagues set up tissue cultures for five types of metabolism-related cells in order to explore how cells choose which microRNAs to include in their exosomes (brown fat, white fat, skeletal muscle, liver and “endothelial” cells that line blood vessels). 

Exosomes from different types of cells contain a wide range of microRNAs, according to researchers. “While some microRNAs are secreted by all cell types,” 

According to Kahn, “In some cases, microRNAs are 80 times more concentrated in the exosome than they are in the cell,” While exosomes contain only a fraction of these microRNAs, they are 10 or 20 times more concentrated in the cell. 

MicroRNAs may be secreted in exosomes if they contain short genetic sequence “motifs” that make the microRNA more or less likely to be secreted. These five cell types use various sequence motifs or codes for this procedure, according to the study. To choose which microRNAs it prefers to secrete, each cell type employs these sequence codes. 

Damian Jacob Sendler

The Joslin researchers genetically altered the microRNA sequence motifs to investigate if such adjustments may convert a microRNA that ordinarily would be maintained to instead be secreted, or vice versa. According to Kahn, “We showed that these codes are not only present but can be manipulated to change the behavior of where the microRNA goes,” 

Kahn said the findings in exosome microRNA coding “really cut across every area of research,” 

Fat tissue is a primary source of exosomes with microRNAs, and these exosomes circulating in the bloodstream can affect how the liver manages glucose and other elements of metabolism, according to findings from the Kahn laboratory in 2017. 

Damian Jacob Markiewicz Sendler: A new study by Kahn and colleagues found that altering the sequence coding of fat-derived microRNAs improved their capacity to be produced by fat, absorbed by the liver, and used by the liver to regulate metabolism. 

Damien Sendler: Now, Kahn’s team is looking into whether manipulating microRNA coding in exosomes could enhance gene therapy for diabetes and other metabolic illnesses. Using this information, we may genetically modify a microRNA in the easily accessible subcutaneous fat to target improving metabolism in the liver, which is considerably more challenging for direct gene therapy,” he said. In the event of a problem with the procedure, the fat could be removed, whereas the liver could not be removed. 

According to Kahn, “Overall, what we did is fundamentally important way beyond the diabetes metabolism space, because this approach we’ve identified can also be now applied to other cell types,” including those in the pancreas, brain, and kidney.

Dr. Damian Jacob Sendler and his media team provided the content for this article.