Pre-vascularization Enhances Therapeutic Effects of Human Mesenchymal Stem Cell Sheets in Full Thickness Skin Wound Repair
AIM Heparanase, a glycohydrolase enzyme, cleaves heparan sulfate in the tissue matrix. Heparan sulfate degradation causes the release of angiogenic and growth factors, leading to angiogenesis. The aim of this paper was to evaluate the angiogenic effect of heparinase-III administration on skin autograft healing in rat. METHODS Four groups of 14 adult male Charles River rats were enrolled. Full thickness skin autografts (15 mm in diameter) were made on the interscapular region of each rat. After 24 hours, 0.1 cc of heparanase, at the three concentrations of 0.1, 0.2, and 0.4 units, were injected intradermally into the grafts of each of the three case groups. The control group received an equal volume of the vehicle (buffered phosphate solution). After 5 days, biopsy specimens from skin grafts of 5 randomly selected rats of each group were submitted for histological studies. RESULTS The concentration of vessels (with 5-50 mm in diameter) in the grafts of the groups receiving 0.2 and 0.4 units of heparanase-III was significantly more than that of the control group (100.43+/-11.24 and 95.85+/-12.44 vs 71.42+/-5.22 vessels/mm(2), P<0.05). The graft survival time of the group that received 0.2 U heparanase-III was significantly longer than that of the control group (15.43+/-0.72 vs 13.23+/-0.69 days; P<0.05). CONCLUSIONS Heparanase-III administration improves the healing of rat skin autografts through induction of angiogenesis.