title: Accelerated healing in NONcNZO10/LtJ type 2 diabetic mice by FGF-1.
abstract: The development of novel therapies to treat chronic diabetic ulcers depends upon appropriate animal models for early stage investigation. The NONcNZO10/LtJ mouse is a new polygenic strain developed to more realistically model human metabolic syndrome and obesity-induced type 2 diabetes; however, detailed wound healing properties have not been reported. Herein, we describe a quantitative wound healing study in the NONcNZO10/LtJ mouse using a splinted excisional wound. The rate of wound healing is compared to various controls, and is also quantified in response to topical administration of normal and mutant fibroblast growth factor-1 (FGF-1). Quantitation of reepithelialization shows that the diabetic condition in the NONcNZO10/LtJ mouse is concomitant with a decreased rate of dermal healing. Furthermore, topical administration of a FGF-1/heparin formulation effectively accelerates reepithelialization. A similar acceleration can also be achieved by a stabilized mutant form of FGF-1 formulated in the absence of heparin. Such accelerated rates of healing are not associated with any abnormal histology in the healed wounds. The results identify the NONcNZO10/LtJ mouse as a useful model of impaired wound healing in type 2 diabetes, and further, identify engineered forms of FGF-1 as a potential “second-generation” therapeutic to promote diabetic dermal wound healing.
authors.forename: Sachiko I
authors.initials: SI
authors.lastname: Blaber
authors.forename: Jose
authors.initials: J
authors.lastname: Diaz
authors.forename: Michael
authors.initials: M
authors.lastname: Blaber
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000473:pathology; D004338:Drug Combinations; D016220:Fibroblast Growth Factor 1 / Q000008:administration & dosage*; D006493:Heparin / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D050505:Mutant Proteins / Q000008:administration & dosage*; D062326:Re-Epithelialization / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012883:Skin Ulcer / Q000209:etiology / Q000473:pathology*; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
chemical_list: D004338:Drug Combinations; D050505:Mutant Proteins; D016220:Fibroblast Growth Factor 1; D006493:Heparin