Revolution in Lung Healing: Penn Vet Researchers' Breakthrough Technique to Repair Damage from Flu and COVID-19
A groundbreaking study by a team of researchers at the University of Pennsylvania has unveiled promising new techniques for repairing lung tissue damaged by illnesses such as the flu and COVID-19. This collaborative effort, crossing multiple disciplines within Penn, represents a significant stride in medical science, potentially changing the way we approach respiratory recovery.
The study, published in the prestigious journal Science Translational Medicine, was spearheaded by Andrew Vaughan of the University of Pennsylvania’s School of Veterinary Medicine. Vaughan and his team focused on the vital role of vascular endothelial cells in lung repair. They discovered that by delivering vascular endothelial growth factor alpha (VEGFA) using lipid nanoparticles (LNPs), they could substantially enhance the repair of damaged blood vessels in the lungs, similar to how plumbers fix and replace broken pipes.
This innovation comes at a crucial time. As the world grapples with the aftermath of respiratory viruses like SARS-CoV-2 and influenza, understanding and improving lung recovery is more important than ever. The lungs' complex network of capillary blood vessels, essential for oxygen and carbon dioxide exchange, can be severely disrupted by such infections, contributing to disease severity and mortality.
Dr. Vaughan's team identified and isolated specific pathways involved in repairing lung tissue. By delivering mRNA to endothelial cells, they observed a notable improvement in the recovery of damaged tissue. "We’ve seen that endothelial cells play a key role in lung repair after viral infections like the flu," Vaughan explains. "Our findings open up new possibilities for more effective lung recovery post-diseases like COVID-19."
The researchers also explored the relationship between VEGFA and the transforming growth factor beta receptor 2 (TGFBR2) signaling pathway. They found that the absence of TGFBR2 hindered the activation of VEGFA, impacting the blood vessel cells' ability to regenerate, a crucial process for efficient lung function.
Partnering with Michael Mitchell of the School of Engineering and Applied Science, renowned for their work in LNPs, the team faced the challenge of delivering this mRNA specifically to lung endothelial cells, bypassing the liver where LNPs typically accumulate. Lulu Xue, a postdoctoral researcher in the Mitchell Lab, developed a novel ionizable lipid that changes its charge upon reaching the endothelial cells, thereby releasing the mRNA.
The results in animal models were remarkable: improved oxygen levels, reduced lung inflammation, and decreased lung damage and scarring, with a healthier vascular network. "It was thrilling to see how effective, safe, and efficient this all panned out," Vaughan remarks, indicating the potential for applying this technology to other lung cell types and conditions such as emphysema and COPD.
The collaboration, involving a diverse group of researchers from Penn Vet, Penn Engineering, and the Perelman School of Medicine at Penn, is a testament to the power of interdisciplinary research. Supported by the National Institutes of Health, the Margaret Q. Landenberger Foundation, the Burroughs Wellcome Fund, and the National Science Foundation, this study paves the way for new mRNA-based strategies for treating lung injuries, heralding a new era in respiratory care and recovery.
