A new mouse model for wound healing in hemophilia A.

ABSTRACT

PURPOSE: To establish a new mouse model for wound healing studies on hemophilia A. METHODS: Total 54 male mice with different genotypes including wild-type nude mice, heterozygous mice (FVIII-/-/Nu) and FVIII deficient mice (FVIII-/-) were generated and verified by PCR. Mice were subjected to wound healing research by making a 5 mm-thickness wound on mice skin and applying recombinant human epidermal growth factor (EGF, 10 µg/g) ointment, FVIII ointment (30 IU) or the ointment base to heal the wounds. Furthermore, keratinocytes were isolated from these newborn mice and subjected to migration assay by stimulation of EGF (ng/ml), insulin (10 µM) or vehicle. RESULTS: A new hemophilic mouse model (FVIII-/-/Nu) was constructed successfully after genotyping verified by PCR. Compared to FVIII-/- mice, FVIII-/-/Nu and Nu mice showed greater degree of wound contraction and loss of the crust. Topical treatment with EGF exhibited faster wound healing than FVIII and ointment base. Insulin treatment showed more increased migration distance than treated with EGF or vehicle. FVIII-/-/Nu mice showed greater migration than FVIII-/- and Nu mice. CONCLUSIONS: A new mouse model (FVIII-/-/Nu) for wound healing in hemophilia A was constructed, and topical treatment of insulin may be a better therapy than EGF for healing wounds in hemophilia A.