Despite advances in wound closure techniques and devices, there is still a critical need for new methods of enhancing the healing process to achieve optimal outcomes. Recently, stem cell therapy has emerged as a new approach to accelerate wound healing. Adipose-derived stem cells (ASCs) hold great promise for wound healing, because they are multipotential stem cells capable of differentiation into various cell lineages and secretion of angiogenic growth factors. The aim of this study was to evaluate the benefit of ASCs on wound healing and then investigate the probable mechanisms. ASCs characterized by flow cytometry were successfully isolated and cultured. An excisional wound healing model in rat was used to determine the effects of locally administered ASCs. The gross and histological results showed that ASCs significantly accelerated wound closure in normal and diabetic rat, including increased epithelialization and granulation tissue deposition. Furthermore, we applied GFP-labeled ASCs on wounds to determine whether ASCs could differentiate along multiple lineages of tissue regeneration in the specific microenvironment. Immunofluorescent analysis indicated that GFP-expressing ASCs were costained with pan-cytokeratin and CD31, respectively, indicating spontaneous site-specific differentiation into epithelial and endothelial lineages. These data suggest that ASCs not only contribute to cutaneous regeneration, but also participate in new vessels formation. Moreover, ASCs were found to secret angiogenic cytokines in vitro and in vivo, including VEGF, HGF, and FGF2, which increase neovascularization and enhance wound healing in injured tissues. In conclusion, our results demonstrate that ASC therapy could accelerate wound healing through differentiation and vasculogenesis and might represent a novel therapeutic approach in cutaneous wounds.

One of the critical responses to insulin treatment is the stimulation of protein synthesis through induced phosphorylation of the eIF-4E-binding protein 1 (4E-BP1), and the subsequent release of the translation initiation factor, eIF-4E. Here we report that ATM, the protein product of the ATM gene that is mutated in the disease ataxia telangiectasia, phosphorylates 4E-BP1 at Ser 111 in vitro and that insulin treatment induces phosphorylation of 4E-BP1 at Ser 111 in vivo in an ATM-dependent manner. In addition, insulin treatment of cells enhances the specific kinase activity of ATM. Cells lacking ATM kinase activity exhibit a significant decrease in the insulin-induced dissociation of 4E-BP1 from eIF-4E. These results suggest an unexpected role for ATM in an insulin-signalling pathway that controls translation initiation. Through this mechanism, a lack of ATM activity probably contributes to some of the metabolic abnormalities, such as poor growth and insulin resistance, reported in ataxia telangiectasia cells and patients with ataxia telangiectasia.

To describe the intramuscular neurovascular anatomy of the rectus femoris muscle and to evaluate whether the muscle can be split into two functional units, 40 rectus femoris muscle specimens were studied. Ten fresh human cadavers were injected with a mixture of lead oxide, gelatin, and water through the femoral arteries. The rectus femoris muscle with its neurovascular pedicles was dissected out and then radiographed. Computer wire was sutured to each nerve branch in the muscle, and the muscle was radiographed again. Radiographs with and without radiopaque wire were then analyzed. In 10 preserved cadavers, the rectus femoris muscle was dissected out. Note was made of the vessel and nerve to the muscle. All muscles were cut serially into 2-cm cross-sections, and the position and course of the intramuscular tendon were then grossly examined. Three different vascular patterns in 40 rectus femoris muscles were found, based on the number of vascular pedicles and their relative dominance within the muscle. The rectus femoris muscle received either a single vascular pedicle (12.5 percent), a dominant vascular pedicle and one or two minor pedicles (80 percent), or two dominant vascular pedicles (7.5 percent). The rectus femoris was innervated by a large nerve branch from the posterior division of the femoral nerve, and the branch generally divided into two sub-branches before it reached the muscle. Both branches were respectively accompanied by arterial branches to form neurovascular hila. Furthermore, this present study has provided a detailed description of the intramuscular neurovascular territories. Also, the pattern of neurovascular supply of the muscle makes it possible to subdivide the muscle into two functional units for segmental muscle transfer.

Control of the translational repressor, PHAS-I, was investigated by expressing proteins with

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Between 1977 and 1993, 64 patients had local muscle flap transposition as an integral portion of treatment for lower-extremity osteomyelitis. All muscle flaps were performed by a single surgeon. There were 54 men and 10 women with an average age of 45 years (range, 16 to 87 years). Median follow-up period was 9.3 years (range, 5 to 21 years). The muscles used included medial gastrocnemius (n = 28), soleus (n = 19), lateral gastrocnemius (n = 13), and peroneus tertius (n = 1). At final follow-up, the recurrence free rates at 5, 10, and 15 years were 94, 92.5, and 86 percent, respectively. These long-term results support the use of local muscle flap transposition as an important management method in the treatment of lower extremity osteomyelitis; however, the risk of treatment failure may arise after extended periods of time.