Researchers at the Icahn School of Medicine at Mount Sinai have created a regenerative medicine treatment to accelerate the healing of diabetic wounds. The therapy involves using small fat particles that are packed with genetic instructions to reduce inflammation. This treatment has been successful in targeting problematic cells and decreasing swelling and harmful molecules in mouse models with damaged skin.
The findings of a study on harmful molecules in mouse models of damaged skin were published in the May 20 online issue of the Proceedings of the National Academy of Sciences (PNAS).
Diabetic wounds, which are often resistant to traditional treatments, are a serious health risk for millions of people worldwide. Instead of helping, immune cells called macrophages end up causing inflammation. This inflammation damages other cells and slows down the healing process.
By using lipid nanoparticles (LNPs) containing RNA that encodes IL-4, a cell signaling molecule, the researchers were able to reduce inflammation in diabetic wounds. This suggests a promising new approach to treating these difficult wounds.
a regenerative phenotype, and the treatment’s capacity to reduce ROS production in diabetic wounds,” said the lead researcher. “This dual effect seems to promote a more favorable environment for wound healing.”
The therapy involved the use of a specific protein that targeted dysfunctional macrophages, which are cells responsible for inflammation. By reprogramming these macrophages, the therapy was able to reduce inflammation and ROS production in diabetic wounds. This dual effect created a more favorable environment for wound healing, as demonstrated in preclinical models.
According to Yizhou Dong, PhD, the lead author of the study and a Professor of Immunology and Immunotherapy at Icahn Mount Sinai, dysfunctional macrophages are responsible for impairing wound healing in diabetic patients. However, their research suggests that these macrophages can be reprogrammed to promote the healing process and improve wound closure. This can lead to faster and more effective wound healing outcomes. In a related study earlier this year, Dr. Dong and colleagues discovered.The study focused on lipid nanoparticles that improved the tissue engineering and regeneration activity of adipose stem cells to treat diabetic wounds (Nature Communications). Although the results of the study are positive, the researchers stress the importance of conducting a rigorous randomized controlled clinical trial to confirm the safety and efficacy in humans. “Our ultimate goal is to translate these findings into tangible benefits for diabetic patients. With further research and validation, this RNA-LNP therapy could potentially revolutionize diabetic wound management with one easily scalable approach.”Dr. Dong stated, “The use of a relatively affordable treatment is an important discovery. The research also indicates the potential for RNA-LNP therapeutics to be more broadly developed to reprogram disease-causing macrophages in an organism, as pro-inflammatory macrophages have been linked to a wide range of diseases.” The other authors of the study are Siyu Wang, PhD (Icahn Mount Sinai); Yuebao Zhang, PhD (Ohio State University); Yichen Zhong, BS (Icahn Mount Sinai); Yonger Xue, PhD (Ohio State University, Icahn Mount Sinai); Zhengwei Liu, PhD (Icahn Mount Sinai); Chang Wang, PhD (Icahn Mount Sinai); Diana D. Kang, PhD (Ohio State University, Icahn Mount Sinai).); Haoyuan Li, MD (Icahn Mount Sinai); Xucheng Hou, PhD (Icahn Mount Sinai); Meng Tian, PhD (Icahn Mount Sinai); Dinglingge Cao, PhD (Icahn Mount Sinai); Leiming Wang, PhD (Icahn Mount Sinai); Kaiyuan Guo, BS (Icahn Mount Sinai); Binbin Deng, PhD (Ohio State University); David W. McComb, PhD (Ohio State University); Miriam Merad, MD, PhD (Icahn Mount Sinai); and Brian D. Brown, PhD (Icahn Mount Sinai).
The research was partly supported by the National Institute of General Medical Sciences grant R35GM144117.
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