The regenerative potential of fibroblasts in a new diabetes‐induced delayed humanised wound healing model

• DOI: 10.1111/exd.12097
• Publication Date: 2013-01-22T11:06:41Z
• Authors: Lucía Martínez‐Sa...; Claudio J. Conti; Sara Llames; Eva García; Luisa Retamosa; Almudena Holguín; Nuria Illera; Blanca Duarte; Lino Camblor; José M. Llaneza; José L. Jorcano; Fernando Larcher; Álvaro Meana; María J. Escámez; Marcela Del Río
• Keywords: 0301 basic medicine; Cutaneous wounds; Time Factors; Mouse; Medicina; Transplantation, Heterologous; Cell- and Tissue-Based Therapy; Mice, Nude; Bioengineering; Streptozocin; Diabetes Mellitus, Experimental; Mice; 03 medical and health sciences; Skin Physiological Phenomena; Animals; Humans; Regeneration; Tissue engineering; Cells, Cultured; Diabetic wounds; Fibrin; Wound Healing; Matrix; Tissue Scaffolds; In-vivo model; Fibroblasts; Engineered skin; Venous leg; Stem-cells; Animal models; 3. Good health; Disease Models, Animal; Foot ulcers; Female; Delayed wound healing

AbstractCutaneous diabetic wounds greatly affect the quality of life of patients, causing a substantial economic impact on the healthcare system. The limited clinical success of conventional treatments is mainly attributed to the lack of knowledge of the pathogenic mechanisms related to chronic ulceration. Therefore, management of diabetic ulcers remains a challenging clinical issue. Within this context, reliable animal models that recapitulate situations of impaired wound healing have become essential. In this study, we established a newin vivohumanised model of delayed wound healing in a diabetic context that reproduces the main features of the human disease. Diabetes was induced by multiple low doses of streptozotocin in bioengineered human‐skin‐engrafted immunodeficient mice. The significant delay in wound closure exhibited in diabetic wounds was mainly attributed to alterations in the granulation tissue formation and resolution, involving defects in wound bed maturation, vascularisation, inflammatory response and collagen deposition. In the new model, a cell‐based wound therapy consisting of the application of plasma‐derived fibrin dermal scaffolds containing fibroblasts consistently improved the healing response by triggering granulation tissue maturation and further providing a suitable matrix for migrating keratinocytes during wound re‐epithelialisation. The present preclinical wound healing model was able to shed light on the biological processes responsible for the improvement achieved, and these findings can be extended for designing new therapeutic approaches with clinical relevance.