Therapeutic nanocarriers engineered from adult skin cells can curb inflammation and tissue injury in damaged mouse lungs, new research shows, hinting at the promise of a treatment for lungs severely injured by infection or trauma.
Researchers conducted experiments in cell cultures and mice to demonstrate the therapeutic potential of these nanoparticles, which are extracellular vesicles similar to the ones circulating in humans’ bloodstream and biological fluids that carry messages between cells.
The hope is that a drop of solution containing these nanocarriers, delivered to the lungs via the nose, could treat acute respiratory distress syndrome (ARDS), one of the most frequent causes of respiratory failure that leads to putting patients on a ventilator. In ARDS, inflammation spiraling out of control in the lungs so seriously burdens the immune system that immune cells are unable to tend to the initial cause of the damage.
“These extracellular vesicles would be an alternative ARDS therapy that gives a fighting chance to your own immune system,” said senior author Natalia Higuita-Castro, associate professor of biomedical engineering and neurosurgery at The Ohio State University. “The issue with ARDS is that you have a shift in the normal balance that favors inflammation. By introducing the anti-inflammatory agents, you shift that balance to a more level stage so the immune system can resolve the underlying issue.”
The study was published online recently in the journal Advanced Materials.
Many nanocarriers are engineered from stem or progenitor cells that can differentiate into other cell types, but also have mysterious properties that aren’t yet fully understood.
To create the vesicles, scientists apply an electrical charge to a donor skin cell to transiently open holes in its membrane, and deliver externally obtained DNA inside. The donor cell converts that genetic information into one of two anti-inflammatory proteins as well as into messenger RNA, molecules that translate instructions for the manufacture of more of those functional proteins.
Those materials are the payload inside these nanocarriers, whose surfaces are tagged with a molecule enabling interaction with specific cells to improve their retention in the lungs. In this study, separate nanocarriers were packed with one of two anti-inflammatory proteins, IL-4 or IL-10, plus mRNA for recipient cells in the lung to process and make more protein.
Cell culture experiments suggested these vesicles could be used as a pre-treatment in sick patients at high risk for developing ARDS. Studies in mice showed their potential to help patients who are already severely ill.
Finding a safe, effective treatment for ARDS is a significant medical need. The current use of ventilators and steroids comes with lots of side effects, and while the dangerous lung condition used to be relatively rare, case numbers skyrocketed during the COVID-19 pandemic.
There is more to do with the nanocarriers, including pinning down the precise details of all they can do to repair damaged lungs and testing the therapy in larger animals. But Higuita-Castro is optimistic about the technology’s future.
Ana I. Salazar‐Puerta, María A. Rincon‐Benavides, Tatiana Z. Cuellar‐Gaviria, Julian Aldana, Gabriela Vasquez Martinez, Lilibeth Ortega‐Pineda, Devleena Das, Daniel Dodd, Charles A. Spencer, Binbin Deng, David W. McComb, Joshua A. Englert, Samir Ghadiali, Diana Zepeda‐Orozco, Loren E. Wold, Daniel Gallego‐Perez, Natalia Higuita‐Castro. Engineered Extracellular Vesicles Derived from Dermal Fibroblasts Attenuate Inflammation in a Murine Model of Acute Lung Injury. Advanced Materials, 2023; DOI: 10.1002/adma.202210579
Ohio State University. (2023, June 6). A lung injury therapy derived from adult skin cells: In mice, naturally derived nanocarriers reduce inflammation, tissue damage. ScienceDaily. Retrieved June 12, 2023 from www.sciencedaily.com/releases/2023/06/230606111722.htm
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