"We knew, then, that the significant anti-inflammatory and protective effects we saw had to be caused by something released by the MSCs," Kourembanas explained. "The question was, what?"
To answer that question, the research team grew mouse MSCs in the laboratory and searched the conditioned media for any secreted factors. They came upon exosomes, which many cell types, including MSCs, produce and release as a kind of communication vehicle.
The team found that injecting just purified exosomes from MSCs reduced lung inflammation and prevented the occurrence of PH in their animal model of PH. In contrast, neither MSC-conditioned media depleted of exosomes nor exosomes purified from other cell types had any effect on inflammation or PH in the model, indicating that something unique to the MSC-produced exosomes is required for their protective effect.
"We are actively working to figure out what exactly within the MSC-produced exosomes causes these anti-inflammatory and protective effects," Kourembanas said. "But we know that these exosomes contain microRNAs as well as other nucleic acids. They also induce expression of specific microRNAs in the recipient lung."
MicroRNAs are small pieces of RNA that regulate gene activity in very specific ways. Thousands of microRNAs have been identified in species up and down the evolutionary tree since their initial discovery in worms nearly 20 years ago, suggesting they play a fundamental role in the cell's regulatory machinery.
"What we may be seeing is the effect of these microRNAs on the expression of multiple genes and the activity of multiple pathways within the lungs and the immune system all at once," she continued.
Looking to the future, Kourembanas thinks exosome research cou
|Contact: Meghan Weber|
Boston Children's Hospital