The effects of embryonic stem cells (ESCs) on diabetic wound healing were investigated using an excisional skin wound model in 110 diabetes-induced rats. We transplanted a clonal population of ESCs (5 Â 10 6 ) by topical injection into full thickness skin wounds. Four study groups were used; nondiabetic rats as a control, non-insulin controlled diabetic rats not treated with ESCs, insulin controlled diabetic rats not treated with ESCs, and insulin controlled diabetic rats treated with ESCs. Five rats in each experimental group were sacrificed on days 1, 5, 10, 15, and 20 after wounding. Wounds images were acquired daily and wound sizes were calculated. We measured the mRNA levels of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF), and fibronectin levels in extracellular matrix, and assessed wound healing by assessing histological parameters of epidermal regeneration, granulation tissue thickness, and angiogenesis. In the ESC-treated group, wound sizes were significantly smaller than in the insulin controlled diabetic group not treated with ESCs on days 5 and 10 (p < 0.05), and EGF and VEGF levels were markedly higher on days 5 and 10, fibronectin levels on day 5 after injection. All histological scores in the ESC-treated group were significantly higher than those of the insulin controlled diabetic group on day 5 (p < 0.05). Our results shows that topical ESCs enhance diabetic wound healing during the early stage, and suggest that ESCs transplantation offers a novel therapeutic modality for the treatment of diabetic wounds. ß

To investigate the developmental pattern of femoral shortening in Legg-Calve-Perthes disease, the authors made an experimental model of the disease in piglets by devascularizing the capital femoral epiphysis and following the piglets to skeletal maturity. The discrepancy first increased in the postoperative 0 to 8 weeks (1.2-1.9 mm of shortening per week), then decelerated for a considerable period during the postoperative 8 to 16 weeks (0.2-0.6 mm per week), and then increased again toward the end of the growth period of the postoperative 20 weeks (1.2 mm per week). The developmental pattern of femoral shortening showed an upward slope/plateau/upward slope pattern, as in type IV of the Shapiro classification. As the mechanism of the observed pattern, the authors presumed reduced epiphyseal height and growth retardation in the physis during the initial upward slope, a repair process at the plateau phase, and premature physeal closure during the second upward slope.