Accelerated healing in NONcNZO10/LtJ type 2 diabetic mice by FGF-1

Wound Repair Regen. Jul-Aug 2015;23(4):538-49. doi: 10.1111/wrr.12305.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Chronic Disease
  • Diabetes Mellitus, Experimental*
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / pathology
  • Drug Combinations
  • Fibroblast Growth Factor 1 / administration & dosage*
  • Heparin / administration & dosage*
  • Male
  • Mice
  • Mutant Proteins / administration & dosage*
  • Re-Epithelialization / drug effects
  • Skin / drug effects
  • Skin / pathology
  • Skin Ulcer / etiology
  • Skin Ulcer / pathology*
  • Treatment Outcome
  • Wound Healing / drug effects
  • Wound Healing / physiology*


  • Drug Combinations
  • Mutant Proteins
  • Fibroblast Growth Factor 1
  • Heparin