Frostbite, a severe cold injury affecting millions globally, can lead to prolonged recovery, scarring, and chronic complications, including pain and functional impairment. The injury typically starts with cold-induced cell death, localized inflammation, and tissue ischemia, disrupting the skin’s ability to heal. While current treatments, such as calcium channel blockers, offer limited success in preventing scarring, they often fail to address the deeper cellular and structural damage. This underscores the urgent need for innovative therapies capable of accelerating recovery and restoring normal skin function.
A promising new approach emerged in a study published on October 4, 2024, by researchers from Peking Union Medical College Hospital and the National Center for Protein Sciences (Beijing). Published in Protein & Cell (DOI: 10.1093/procel/pwae055), the research investigates the potential of human-induced pluripotent stem cell (hiPSC)-derived skin organoids to treat frostbite injuries and promote scarless wound healing.
The team developed a mouse model of frostbite to examine the healing process at a cellular level. Using single-cell transcriptomics, they tracked changes in cell types such as monocytes, macrophages, epidermal cells, and fibroblasts. The analysis revealed early-stage frostbite characterized by inflammation, immune cell infiltration, and extracellular matrix (ECM) disruption. To combat this, the researchers engineered hiPSC-derived skin organoids and combined them with gelatin-hydrogel, which were then transplanted into frostbite-injured mice.
The results were promising: the skin organoids significantly accelerated healing by reducing early inflammation through the suppression of inflammatory cytokines like CCL4 and IL6. Furthermore, they promoted the proliferation of epidermal stem cells. Later in the healing process, the organoids regulated the integrin α5β1-FAK pathway, preventing fibroblast transformation into myofibroblasts and aiding in ECM remodeling. This process minimized abnormal scarring and restored the physiological ECM, paving the way for scarless healing.
Dr. Ling Leng, a corresponding author of the study, emphasized the importance of these findings, stating, “Our study demonstrates that skin organoids can effectively modulate the inflammatory response and promote rapid wound healing in frostbite injuries. This opens up new possibilities for treating complex wounds and preventing long-term complications.”
This breakthrough marks a significant advancement in regenerative medicine. By accelerating healing and preventing scar formation, skin organoids offer a potential game-changer for patients with severe frostbite. Their ability to modulate inflammation and restore skin function addresses a critical gap in current treatments, which often overlook long-term recovery challenges. Future research will aim to refine skin organoid transplantation techniques and explore their potential in treating other complex skin conditions, such as burns and chronic wounds. This breakthrough not only holds promise for frostbite care but also offers a new avenue for improving patient outcomes and quality of life in a wide range of skin injuries.
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