In a groundbreaking study published in the Proceedings of the National Academy of Sciences (PNAS), researchers at the Icahn School of Medicine at Mount Sinai have designed a novel regenerative medicine therapy aimed at accelerating the repair of diabetic wounds. The therapy utilizes tiny fat particles, known as lipid nanoparticles, loaded with genetic instructions in the form of RNA encoding IL-4, a cell-to-cell signaling protein, to calm inflammation and promote healing.
Diabetic wounds, which often prove resistant to conventional treatments, pose significant health risks to millions of individuals worldwide. The healing process is hindered by immune cells called macrophages, which, instead of aiding in repair, contribute to inflammation. This inflammation damages other cells and impedes the wound's ability to heal efficiently and effectively.
The LNP-based therapy developed by the Mount Sinai researchers targets these dysfunctional macrophages while simultaneously reducing inflammation and harmful molecules known as reactive oxygen species in diabetic wounds. ROS molecules, produced naturally during various metabolic processes, play essential roles in cell signaling and immune responses. However, excessive ROS production can lead to oxidative stress, causing damage to cells, proteins, and DNA, and is associated with various diseases and conditions, including inflammation and aging.
Yizhou Dong, PhD, the corresponding author of the study and a Professor of Immunology and Immunotherapy at Icahn Mount Sinai, emphasized the therapy's potential to reprogram pro-inflammatory macrophages into reparative ones. "Dysfunctional macrophages drive diabetic non-healing wounds, but we can reprogram them to stop the damage and instead help the healing process," stated Dr. Dong. "We aim to promote faster and more effective wound closure by reprogramming these cells and modulating the inflammatory environment."
The preclinical models used in the study demonstrated the therapy's ability to improve wound healing outcomes by reprogramming macrophages and reducing inflammation. Earlier this year, in a related study, Dr. Dong and colleagues reported on lipid nanoparticles that enhanced the tissue engineering and regeneration activity of adipose stem cells for treating diabetic wounds.
While the results of the current study are promising, the researchers stress the need for rigorous randomized controlled clinical trials to confirm the therapy's safety and efficacy in humans. Dr. Dong expressed the ultimate goal of translating these findings into tangible benefits for diabetic patients, stating, "With further research and validation, this RNA-LNP therapy could potentially revolutionize diabetic wound management with one easily scalable application of a comparatively inexpensive therapeutic agent."
The study also suggests the potential for RNA-LNP therapeutics to be more generally designed to reprogram disease-causing macrophages in an organism, as pro-inflammatory macrophages are implicated in a wide range of diseases. The remaining authors of the study include researchers from the Icahn School of Medicine at Mount Sinai and Ohio State University.
The study, titled "Accelerating diabetic wound healing by ROS-scavenging lipid nanoparticle-mRNA formulation," was funded in part by the National Institute of General Medical Sciences grant R35GM144117. The development of this innovative regenerative medicine therapy marks a significant step forward in the treatment of diabetic wounds and offers hope for millions of individuals suffering from this debilitating condition.
