A New Diabetic Skirt-Humanized Mouse Model Unravels the Regenerative Potential of Fibroblasts in Impaired Healing Process

Diabetes is a systemic disorder with a high incidence continuously increasing. Impaired wound healing is one of the major complications associated to diabetes since about 15% of all diabetic patients develop an ulcer on the foot or the leg during the course of their illness. Animal models have been used extensively in diabetes research. However, the need to design appropriate models in a humanized context that recapitulate situations of impaired wound healing has become mandatory to explore the usefulness of new therapies for sanitary problems such as chronic ulcers in diabetics. To this end, we have developed a new model of diabetes-induced wound healing impairment in the skin-humanized mice that exhibits a delayed fibrinolysis involving defects in the vascu-lature, granulation tissue, inflammatory response and dermal innervation. In summary, the proposed model recapitulates the vasculopathy and the peripheral neuropathy, main factors related to diabetic ulcers in patients. Consequently, this system has been useful to get a better understanding of the mechanisms underlying diabetes wound repair impairment and may represent a valuable preclinical platform to test new therapeutic approaches. One of such strategies is based on the use of bioengineered dermal equivalents. At the preclinical stage, a dramatic overall improvement of the healing process was achieved by the treatment of diabetic wounds with fibroblast-enriched fibrin-based dermal scaffolds. Preliminary data from a pilot study in diabetic patients strongly suggests that allogenic fibroblasts administered as part of a dermal substitute play a pivotal role on skin regeneration.