Second-degree burn wounds treated in a phase 1/2a clinical study with mesenchymal stem cell-derived extracellular vesicles (EVs) exhibit enhanced regenerative healing

Summary: Burn injuries pose challenges in immediate recovery and long-term scarring outcomes, leading to significant morbidity, and traditional treatments have yielded limited success in inhibiting burn wound conversion, restoring skin architecture, or preventing contractures. Mesenchymal stem cells (MSCs) have shown promise in wound healing, and recent research suggests that MSC-secreted extracellular vesicles (EVs) could be key to these regenerative effects. EVs deliver nucleic acids and proteins, reducing oxidative stress, inhibiting neutrophil activation, and preventing ischemia-reperfusion injury. A 47-year-old Hispanic male patient with gasoline fire burns was treated as part of a Phase 1/2a first-in-human, prospective, open-label study administering allogeneic MSC-derived EVs to deep second-degree burn wounds within 48 hours of injury. After just 1 treatment, the wound exhibited >99% closure at 1-week post-injury and remained durably closed through 1 year of follow-up. Furthermore, scores on the POSAS (Patient/Observer Scar Assessment Scale) markedly decreased over 52 weeks (week 4 - no pain; week 8 - no itch; no scarring). These results were in contrast with typical burn wounds which can take 4-6 weeks to close and result in poor scarring outcomes. The primary objective was to assess the safety of allogeneic MSC-derived EVs, and no adverse events were observed. Additionally, EVs prevented conversion of second-degree burns to third-degree burns as laser doppler imaging showed early restoration of skin perfusion after just 1 week. In summary, initial results from our study suggest that EVs can serve as a treatment to enhance burn recovery and reduce the long-term morbidity associated with burn scars. Aaron Gabriel Sandoval^{4, 3}, Carl I. Schulman², Louis Pizano², Nicholas Namias², Gloria Matthews³, Shelley Hartman³, Evangelos Badiavas^{1, 3} 1. Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, United States. 2. Department of Surgery, Ryder Trauma Center, University of Miami Miller School of Medicine, Miami, FL, United States. 3. Aegle Therapeutics, Woburn, MA, United States. 4. Harvard Medical School, Boston, MA, United States. Clinical Research: Interventional Research