Transplantation of the LGR6+ epithelial stem cell into full-thickness cutaneous wounds results in enhanced healing, nascent hair follicle development, and augmentation of angiogenic analytes.

BACKGROUND: The recently discovered leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6+) epithelial stem cell located within the follicular bulge of the adnexal compartment is capable of producing all cellular lineages of the skin. In this study, the authors sought to determine whether these cells can be transplanted for use as a type of cellular therapy for the repair of full-thickness wounds in which the native stem cell niche has been obliterated. METHODS: Full-thickness murine skin was harvested and LGR6(+GFP) epithelial stem cells were isolated using fluorescence-activated cell sorting. This enriched epithelial stem cell population was then transplanted by means of local injection into wound beds on the dorsum of nude mice. Viability, migration, healing, the development of nascent hair follicles, and gene and proteomic expression studies were performed to determine whether the engraftment of LGR6(+GFP) epithelial stem cells enhanced healing when compared with controls. RESULTS: Wound beds receiving LGR6(+GFP) epithelial stem cells showed enhanced healing; nascent follicle growth; and augmentation of the Wnt, vascular endothelial growth factor, epidermal growth factor, and platelet-derived growth factor pathways when compared with controls. CONCLUSIONS: The LGR6+ epithelial stem cells appear to hold great promise for the development of a clinically useful stem cell­based therapy for the repair of full-thickness wounds and hair regeneration. These results indicate that transplantation of LGR6+ epithelial stem cells promotes epithelialization, hair growth, and angiogenesis in tissues destined for scar formation.

Neurotrophin expression of laryngeal muscles in response to recurrent laryngeal nerve transection.

OBJECTIVE/HYPOTHESIS: The recurrent laryngeal nerve (RLN) commonly regenerates after injury; however, functional motion is rarely recovered. Animal experiments have documented aberrant reinnervation after nerve transection, with motor axons reaching inappropriate muscles. More recently, experimental results suggest that lack of vocal fold motion after RLN injury is due to preferential reinnervation of adductor muscles, with inadequate reinnervation of the posterior cricoarytenoid muscle (PCA), the only abductor muscle of the larynx. Information on factors that could influence the receptiveness of these muscles to reinnervation could be useful in developing new therapeutic strategies. It is hypothesized that the thyroarytenoid muscle (TA) and the PCA differ in expression of neurotrophins in response to denervation. STUDY DESIGN: Laboratory experiment. METHODS: Rats were sacrificed at 3 days, 6 weeks, or 4 months after unilateral RLN injury measure expression of brain-derived nerve growth factor (BDNF), nerve growth factor (NGF), and neurotrophin 4 (NT-4) in the TA and PCA muscles, using immunohistochemistry. We also assessed nerve regeneration. RESULTS: NGF was significantly diminished in the denervated TA muscle at 3 days after injury and increased at 6 weeks. BDNF expression was unchanged in the TA, but was diminished in both PCA muscles at 3 days and 6 weeks, returning to near-normal levels at 4 months after injury. Robust nerve regeneration of distal RLN was present at 4 months. CONCLUSIONS: Results suggest that the TA and PCA muscles respond differently to denervation.