Adipose-Derived Stem Cells Enhance Axonal Regeneration through Cross-Facial Nerve Grafting in a Rat Model of Facial Paralysis.

BACKGROUND: Cross-face nerve grafting combined with functional muscle transplantation has become the standard in reconstructing an emotionally controlled smile in complete irreversible facial palsy. However, the efficacy of this procedure depends on the ability of regenerating axons to breach two nerve coaptations and reinnervate endplates in denervated muscle. The current study tested the hypothesis that adipose-derived stem cells would enhance axonal regeneration through a cross-facial nerve graft and thereby enhance recovery of the facial nerve function. METHODS: Twelve rats underwent transection of the right facial nerve, and cross-facial nerve grafting using the sciatic nerve as an interpositional graft, with coaptations to the ipsilateral and contralateral buccal branches, was carried out. Rats were divided equally into two groups: a grafted but nontreated control group and a grafted and adipose-derived stem cell-treated group. Three months after surgery, biometric and electrophysiologic assessments of vibrissae movements were performed. Histologically, the spectra of fiber density, myelin sheath thickness, fiber diameter, and g ratio of the nerve were analyzed. Immunohistochemical staining was performed for the evaluation of acetylcholine in the neuromuscular junctions. RESULTS: The data from the biometric and electrophysiologic analysis of vibrissae movements, immunohistochemical analysis, and histologic assessment of the nerve showed that adipose-derived stem cells significantly enhanced axonal regeneration through the graft. CONCLUSION: These observations suggest that adipose-derived stem cells could be a clinically translatable route toward new methods to enhance recovery after cross-facial nerve grafting.

The Notch pathway is a critical regulator of angiogenesis in a skin model of ischemia.

The Notch pathway is definitely required for normal vascular development. Although the contribution of Notch in postnatal angiogenesis is the focus of intense investigation, the implication of Notch in reparative neovascularization in the skin remains unexplored. In this study, we investigated Notch changes using a skin model of ischemia. Thirty Sprague-Dawley rats were divided into two groups. In the surgery group (n = 24), a caudally based dorsal skin flap was raised and sutured back into its initial position. In the control group, no surgical procedure was performed. Tissue biopsies were obtained at different time intervals. Tissue specimens were assessed for Delta-like ligand 4 (DLL4) and vascular endothelial growth factor (VEGF) gene expression by real-time polymerase chain reaction (PCR). Immunohistochemical staining was used for detection of DLL4 in tissue materials. Quantitative assessment of skin flap microvasculature was made. Compared with normoperfused tissue, VEGF and DLL4 expressions increased significantly (p < 0.01). Immunohistochemical analysis revealed weak and patchy expression of DLL4 in microvascular endothelial cells of normoperfused tissues. Conversely, DLL4 expression was upregulated in capillary endothelial cells after ischemia. In conclusion, in this study we have shown that the Notch ligand DLL4 is upregulated in skin tissue after ischemia. A deeper understanding of these fundamental principles will aid in the development of new avenues for the treatment of blood vessel-related skin pathologies.

An in vivo comparison of commonly used topical antimicrobials on skin graft healing after full-thickness burn injury.

Topical antimicrobials are frequently used for local control of infections in burn patients. It has been postulated that these agents retard wound healing. There are limited data about the effects of topical antimicrobial agents on skin graft healing. In this study, we aimed to evaluate the effects of nitrofurazone, 1% silver sulfadiazine, and povidone-iodine on skin graft healing. Forty male rats were used in this study. A meshed skin graft, placed on an excised burn wound, was used as a model to compare topical agents with a control group. Skin graft survival rates, closure of meshed graft interstices (based on physical parameters, namely epithelialization and wound contraction), and histological changes were analyzed. Graft take was more than 85% in all groups. There was no difference between the mean values of the percent graft survival for each group (P > .05). Epithelialization occurred significantly earlier in animals in the nitrofurazone group (P < .05). There was no significant difference between groups in wound contraction rates (P >.05). There was no histological difference between the biopsy specimens of skin grafts. In specimens obtained from the interstices of the meshed graft, no significant differences were found among the groups regarding the wound healing parameters (P > .05). We found that nitrofurazone, silver sulfadiazine, and povidone-iodine had no negative effect on graft healing and take in noncontaminated burn wounds.