Introduction. Diabetes mellitus (DM) is a serious, chronic metabolic disorder commonly complicated by diabetic
foot ulcers with delayed healing. Metformin was found to have a wound healing effect through several
mechanisms. The current study investigated the effect of both bone marrow-derived mesenchymal stem cells
(BM-MSCs) and metformin, considered alone or combined, on the healing of an experimentally induced cutaneous
wound injury in streptozotocin-induced diabetic rats.
Material and methods. Forty adult male albino rats were used. Diabetes was induced by single intravenous (IV)
injection of streptozotocin (STZ). Next, two circular full thickness skin wounds were created on the back of the
animals, then randomly assigned into 4 groups, ten rats each. BM-MSCs were isolated from albino rats, 8 weeks
of age and labeled by PKH26 before intradermal injection into rats of Group III and IV. Groups I (diabetic
positive control), II (metformin-treated, 250 mg/kg/d), III (treated with 2×106 BM-MSCs), and IV (wounded rats
treated both with metformin and BM-MSCs cells). Healing was assessed 3, 7, 14, and 21 days post wound induction
through frequent measuring of wound diameters. Skin biopsies were obtained at the end of the experiment.
Results. Gross evaluation of the physical healing of the wounds was done. Skin biopsies from the wound areas
were processed for hematoxylin and eosin (H&E), Masson’s trichrome staining and immunohistochemical
staining for CD31. The results showed better wound healing in the combined therapy group (IV) as compared
to monotherapy groups.
Conclusions. Although both metformin and BM-MSCs were effective in the healing of experimentally induced
skin wounds in diabetic rats, the combination of both agents appears to be a better synergistic option for the
treatment of diabetic wound injuries. |
