Rise of stem cell therapies in aesthetics.

Stem cells have the ability to self-renew and differentiate into other cell types, which forms the foundation for their use in regenerative medicine and cosmetic dermatology. Adipose-derived stem cells have proven particularly attractive in aesthetics given their relative ease of collection and abundance. Stem cells have been employed for the treatment of androgenetic alopecia and skin rejuvenation with promising results, but their incorporation into cosmeceuticals is still in its infancy. Despite promising preclinical data and small clinical studies, additional randomized, controlled trials and standardization of treatment are needed to truly understand the place of stem cells in the aesthetics arena. We review the current literature and discuss current controversies and debates.

Platelet-Rich Plasma and Stem Cells for Hair Growth: A Review of the Literature.

The prevalence of hair loss, its psychological consequences, and historically subpar treatments present a unique challenge to the physician. The current Food and Drug Administration-approved treatments for hair loss are plagued by ineffectiveness, noncompliance, and adverse effects. Recent advances in our understanding of hair physiology have fueled the development of more efficacious, minimally invasive, and safer treatment options for hair restoration including plasma-rich protein and stem cell therapy. Platelet-rich plasma, the autologous preparation of concentrated platelets in plasma, when injected into the scalp of patients with both androgenetic alopecia (AGA) and alopecia areata (AA), has been shown to increase hair count and density. The clinical findings have been supported by histologic evaluation of the scalp skin. These findings have been recapitulated in numerous randomized controlled trials. Stem cell therapy, although newer in its application in hair restoration, has also been effective for treating both AGA and AA. The isolation techniques for stem cells are varied, but regardless have shown promising results in early prospective and retrospective studies.

The Effect of Negative Pressure Wound Therapy With Antiseptic Instillation on Biofilm Formation in a Porcine Model of Infected Spinal Instrumentation.

OBJECTIVE: This study evaluates the effect of negative pressure wound therapy with antiseptic instillation (NPWTi) in the clearance of infection and biofilm formation in an in vivo model of infected spinal implants compared to traditional treatment modalities. MATERIALS AND METHODS: Five pigs underwent titanium rod implantation of their spinous processes followed by injection of 1 x 106 CFUs/100µL of methicillin-resistant Staphylococcus aureus through the fascia at each site. At 1 week postoperatively, an experimental arm of 3 pigs received NPWTi, and a control arm of 2 pigs received wet-to-dry dressings. The persistence of local infection in the experimental group was compared to the control group using tissue cultures. Biofilm development on spinal implants was evaluated using scanning electron microscopy. RESULTS: Mean bacterial count showed a statistical difference between the experimental and the control groups (P < .05). Scanning electron microscopy revealed the presence of uniform biofilm formation across the surface of control group instrumentation, whereas the experimental group showed interrupted areas between biofilm formations. CONCLUSION: The authors concluded that NPWTi is associated with decreased bacterial load and biofilm formation compared to wet-to-dry dressings in an in vivo porcine model of infected spinal instrumentation.

Closed Incision Negative-Pressure Therapy Is Associated with Decreased Surgical-Site Infections: A Meta-Analysis.

BACKGROUND: Negative-pressure therapy has recently been used over closed incisions to decrease surgical-site occurrences, including infection and dehiscence. A meta-analysis was performed to evaluate the effectiveness of closed incision negative-pressure therapy in lowering the incidence of surgical-site infections compared with standard dressings. METHODS: A literature search was conducted to find publications comparing closed incision negative-pressure therapy to standard incisional care. A fixed-effects model was used to assess between-study and between-incision location subgroup heterogeneity and effect size. Funnel plots were used to assess publication bias. RESULTS: The overall weighted average rates of surgical-site infection in the closed incision negative-pressure therapy and control groups were 6.61 percent and 9.36 percent, respectively. This reflects a relative reduction in surgical site infection rate of 29.4 percent. A decreased likelihood of surgical-site infection was evident in the closed incision negative-pressure therapy group compared with the control group across all studies, and across all four incision location subgroups. Across all studies, odds of surgical-site infections decreased 0.564 (p < 0.00001). After excluding groin incision studies because of heterogeneity following sensitivity analysis, the odds of surgical-site infection decrease was still 0.496 (p < 0.00001). In addition, overall rates of dehiscence in closed incision negative-pressure therapy and control groups were 5.32 percent and 10.68 percent, respectively. CONCLUSIONS: The results of this meta-analysis suggest that closed incision negative-pressure therapy is a potentially effective method for reducing surgical-site infections. It also appears that closed incision negative-pressure therapy may be associated with a decreased incidence of dehiscence, but the published data available were too heterogeneous to perform meta-analysis.

GnRH-(1-5) transactivates EGFR in Ishikawa human endometrial cells via an orphan G protein-coupled receptor.

The decapeptide GnRH is known for its central role in the regulation of the hypothalamo-pituitary-gonadal axis. In addition, it is also known to have local effects within peripheral tissues. The zinc metalloendopeptidase, EC 3.4.24.15 (EP24.15), can cleave GnRH at the Tyr(5)-Gly(6) bond to form the pentapeptide, GnRH-(1-5). The central and peripheral effect of GnRH-(1-5) is different from its parent peptide, GnRH. In the current study, we examined the effect of GnRH-(1-5) on epidermal growth factor receptor (EGFR) phosphorylation and cellular migration. Using the Ishikawa cell line as a model of endometrial cancer, we demonstrate that GnRH-(1-5) stimulates epidermal growth factor release, increases the phosphorylation of EGFR (P < .05) at three tyrosine sites (992, 1045, 1068), and promotes cellular migration. In addition, we also demonstrate that these actions of GnRH-(1-5) are mediated by the orphan G protein-coupled receptor 101 (GPR101). Down-regulation of GPR101 expression blocked the GnRH-(1-5)-mediated release of epidermal growth factor and the subsequent phosphorylation of EGFR and cellular migration. These results suggest that GPR101 is a critical requirement for GnRH-(1-5) transactivation of EGFR in Ishikawa cells.

ß-Arrestin 2 is a mediator of GnRH-(1-5) signaling in immortalized GnRH neurons.

We have previously demonstrated that the cleavage product of the full-length GnRH, GnRH-(1-5), is biologically active, binds G protein-coupled receptor 173 (GPR173), and inhibits the migration of cells in the immortalized GnRH-secreting GN11 cell. In this study, we attempted to characterize the GnRH-(1-5) intracellular signaling mechanism. To determine whether the signaling pathway mediating GnRH-(1-5) regulation of migration involves a G protein-dependent mechanism, cells were treated with a generic G protein antagonist in the presence and absence of GnRH-(1-5), and a wound-healing assay was conducted to measure migration. G Protein antagonist 2 treatment abolished the GnRH-(1-5) inhibition of migration, indicating that the mechanism of GnRH-(1-5) is G protein coupled. To identify the potential Gα-subunit recruited by GnRH-(1-5) binding GPR173, we measured the second messengers cAMP and inositol triphosphate levels. GnRH-(1-5) treatment did not alter cAMP levels relative to cells treated with vehicle or forskolin, suggesting that GnRH-(1-5) does not couple to the Gαs or Gαi subunits. Similarly, inositol triphosphate levels remained unchanged with GnRH-(1-5) treatment, indicating a mechanism not mediated by the Gαq/11 subunit. Therefore, we also examined whether GnRH-(1-5) activating GPR173 deviated from the canonical G protein-coupled receptor signaling pathway by coupling to ß-arrestin 1/2 to regulate migration. Our coimmunoprecipitation studies indicate that GnRH-(1-5) induces the rapid interaction between GPR173 and ß-arrestin 2 in GN11 cells. Furthermore, we demonstrate that this association recruits phosphatase and tensin homolog to mediate the downstream action of GnRH-(1-5). These findings suggest that the GnRH-(1-5) mechanism deviates from the canonical G protein-coupled receptor pathway to regulate cell migration in immortalized GnRH neurons.

The Novel Actions of the Metabolite GnRH-(1-5) are Mediated by a G Protein-Coupled Receptor.

The gonadotropin-releasing hormone (GnRH) was originally isolated from the mammalian hypothalamus for its role as the primary regulator of reproductive function. Since its discovery, GnRH has also been shown to be located in non-hypothalamic tissues and is known to have diverse functions. Although the regulation of GnRH synthesis and release has been extensively studied, there is additional evidence to suggest that the processing of GnRH to the metabolite GnRH-(1-5) represents another layer of regulation. The focus of this review will be on the current evidence for the action of the pentapeptide metabolite GnRH-(1-5) in regulating cellular migration. We discuss the potential role of GnRH-(1-5) in regulating GnRH neuronal migration during development. Furthermore, we demonstrate these actions are mediated by the activation of a G protein-coupled receptor. Our findings suggest that GnRH-(1-5) may play a developmental function in addition to regulating developing cells.

Identification of hypothalamic neuron-derived neurotrophic factor as a novel factor modulating appetite.

Disruption of finely coordinated neuropeptide signals in the hypothalamus can result in altered food intake and body weight. We identified neuron-derived neurotrophic factor (NENF) as a novel secreted protein through a large-scale screen aimed at identifying novel secreted hypothalamic proteins that regulate food intake. We observed robust Nenf expression in hypothalamic nuclei known to regulate food intake, and its expression was altered under the diet-induced obese (DIO) condition relative to the fed state. Hypothalamic Nenf mRNA was regulated by brain-derived neurotrophic factor (BDNF) signaling, itself an important regulator of appetite. Delivery of purified recombinant BDNF into the lateral cerebral ventricle decreased hypothalamic Nenf expression, while pharmacological inhibition of trkB signaling increased Nenf mRNA expression. Furthermore, recombinant NENF administered via an intracerebroventricular cannula decreased food intake and body weight and increased hypothalamic Pomc and Mc4r mRNA expression. Importantly, the appetite-suppressing effect of NENF was abrogated in obese mice fed a high-fat diet, demonstrating a diet-dependent modulation of NENF function. We propose the existence of a regulatory circuit involving BDNF, NENF, and melanocortin signaling. Our study validates the power of using an integrated experimental and bioinformatic approach to identify novel CNS-derived proteins with appetite-modulating function and reveals NENF as an important central modulator of food intake.