Pressure ulcers: description of a new model and use of mesenchymal stem cells for repair

Background: Pressure ulcers (PUs) still represent a heavy burden on many patients and nursing institutions. Our understanding of the pathophysiology and development of new treatments are hampered by the scarcity of suitable animal models.

Objective: Evaluation of the translational value of an easily accessible mouse model.

Methods: PUs were induced by application of magnetic devices on the dorsal skin of mice, which causes localized ischemia. The extent of the lesions and healing rate were quantified. Variations in ischemic exposure time were compared in hairless and normal mice. A detailed histological analysis of regeneration is presented. The influence of streptozotocin-induced diabetes, skin X-irradiation and treatment of the ulcers with human mesenchymal stem cells (MSCs) was investigated using immunodeficient NOD/SCID mice.

Results: Ulcers induced by this form of ischemia have many features in common with decubitus ulcers in humans. No difference between hairy and hairless mice was observed in the rate of healing of the PUs. Unexpectedly, healing was not delayed in diabetic mice, but skin X-irradiation prior to ischemia resulted in a doubling of the time to complete closure of the PUs, and delayed repair of the dermis and panniculus carnosus muscle. Intradermal transplantation of human MSCs did not accelerate healing. The grafted MSCs were short-lived and only marginally participated in regeneration by differentiating into tissue-specific cells.

Conclusion: The results emphasize the difference in the characteristics of PUs as compared to surgical wounds. This experimental model is recommended for preclinical research on decubitus ulcers because of its mechanistic similarity with clinical PUs and its simplicity.