A prospective, open label, multicenter, postmarket study evaluating Princess VOLUME Lidocaine for the correction of nasolabial folds.

The aim of this study was to investigate the safety and performance of Princess VOLUME Lidocaine in nasolabial fold correction. In this prospective, open label, multicenter, postmarket study subjects received injections of Princess VOLUME Lidocaine into both NLF at Baseline (Day 0) and if considered necessary by the investigator, at Week 2 (touch-up treatment). This study was conducted in Austria at the Department of Dermatology and Venereology, Medical University of Graz, at the medical aesthetic center MÄZ WIEN, and at the medical aesthetic center Ordination Dr. Bartsch, Vienna. The 62 mainly female (95.2%) subjects had a median age of 52 years with two fully visible, approximately symmetrical NLFs, each scoring grade 2 or 3 on the nasolabial fold severity rating scale (NLF-SRS) developed by Croma-Pharma. The nasolabial fold severity was assessed by NLF-SRS and Global Aesthetic Improvement Scale (GAIS) 4, 24, and 36 weeks later. Adverse events (AEs) were recorded throughout the investigation. With 95.1% of subjects showing an improvement of at least 1 grade of the NLF-SRS at 24 weeks after the treatment, the primary endpoint was achieved, and clinical performance was demonstrated. Princess VOLUME Lidocaine was well tolerated, with only mild AEs, mainly injection site reactions, reported. Subject satisfaction (≥93.5%) and GAIS scores (≥93.5% improvement) were high. Princess VOLUME Lidocaine was effective in reducing NLFs as shown by an improvement in the severity of NLFs by at least one grade in 95.1% of subjects at Weeks 4 and 24.

Safety And Efficacy Of Princess® FILLER Lidocaine In The Correction Of Nasolabial Folds.

PURPOSE: Nasolabial folds (NLFs) are one of the most noticeable signs of facial aging. NLFs negatively affect self-confidence and social acceptance often leading to a person's desire to improve their appearance using dermal fillers. The hyaluronic acid injectable gel implant Princess® FILLER Lidocaine (PFL) is a minimally invasive easy to administer the product. In this investigation, we assessed the safety and efficacy of PFL to correct moderate to severe NLFs over a 36-week period. METHODS: Adult women and men with moderate to severe NLFs received one injection of PFL to both NLFs. After 2 weeks, a touch-up treatment could be performed, if deemed necessary by the investigator. The change in NLF severity was assessed using the Nasolabial Fold Severity Rating Scale (NFL-SRS) developed by Croma-Pharma and the Global Aesthetic Improvement Scale (GAIS). RESULTS: Out of 60 analyzed subjects, 59 (98.3%) had improved their NLF severity by at least 1 grade on the NFL-SRS at week 4, 58 subjects (96.7%) at weeks 24 and 36. All subjects showed aesthetic improvement (GAIS), at weeks 4 and 24. The investigator judged the aesthetics as very much improved (score of 1) in 45 (75.0%) at week 4, 48 (80.0%) at week 24, and in 39 of 60 subjects, respectively (65.0%) at week 36. Thirty-six weeks post-initial treatment, 56 of 60 subjects (93.3%) were very satisfied or satisfied with the treatment. Adverse device effects (ADEs) were mild or moderate and resolved at latest 25 days post-onset. The most commonly reported ADEs were injection site hematoma and injection site pain. CONCLUSION: PFL was safe and effective in reducing the severity of NLFs. Most subjects were (very) satisfied with the treatment outcome throughout a 36 weeks investigation period.

Sheep Placenta Cotyledons: A Noninvasive Source of Ovine Mesenchymal Stem Cells.

Sheep are one of the most frequently used large animal models in stem cell research. However, minimal invasive or noninvasive sources of mesenchymal stem cells (MSCs) in sheep are scarce. In the light of the principles of the 3Rs (reduce, refine, replace), it would therefore be desirable to identify a minimally invasive or noninvasive ovine MSC source. In humans, the chorionic villi of the placenta, which can be noninvasively harvested as part of the afterbirth, have been identified as a rich source of MSCs. Therefore, in the present study, ovine placenta cotyledons, which have similar function and structure to human chorionic villi, were tested for their potential use as a noninvasive source of ovine MSCs. Through mincing of the placental cotyledons, collagenase digestion, and Ficoll density gradient centrifugation, combined with plastic adherence selection, MSCs were successfully isolated. Their morphological, immunophenotypical, and cellular growth characteristics, as well as their proliferation, differentiation, and migration potential, were evaluated and compared to the currently best-researched MSC source, bone marrow-derived stem cells. Ovine cotyledons were shown to be a reliable, abundant source for the noninvasive, pain- and risk-free harvest of MSCs. The collection procedure does not interfere with partum or the initial bonding phase between ewes and lambs and is therefore exempt from ethical debate. Ovine placenta cotyledon-derived MSCs exhibit multipotential characteristics and can be cryopreserved for later use.

Autocrine IL-10 partially prevents differentiation of neonatal dendritic epidermal leukocytes into Langerhans cells.

To test whether reduced immune responsiveness in early life may be related to the immaturity of neonatal antigen-presenting cells, we comparatively assessed the phenotypic and functional characteristics of dendritic epidermal leukocytes (DEL) and epidermal Langerhans cells (LC) in newborn (NB) and adult mice, respectively. We report that purified, 3-day-cultured DEL do not acquire the morphology and phenotype typical of LC and are significantly weaker stimulators of naive, allogeneic CD4+ and CD8+ T cells than LC. Freshly isolated DEL are twice as efficient as LC in the uptake of fluorescein isothiocyanate-conjugated tracers but are not able to present these to antigen-specific T cell hybridomas. To clarify the underlying cause, cytokine expression of NB and adult epidermal cells (EC) was examined. We found that DEL express considerable amounts of interleukin (IL)-10, that IL-10 in NB EC supernatants partially inhibits LC maturation, and that DEL-enriched EC from IL-10-/- mice induce stronger primary T cell responses compared with those from IL-10+/+ mice. We conclude that IL-10 is one of the factors preventing maturation and differentiation of DEL into immunocompetent LC in intrauterine life and is at least partly responsible for the poor immune responsiveness of neonates.

Ontogeny of Langerin/CD207 expression in the epidermis of mice.

C-type lectin receptors help Langerhans cells (LC) to take up and process pathogens. Langerin/CD207 is a mannose-binding C-type lectin that is specifically expressed by LC. It is involved in antigen uptake in an as yet poorly defined way, and it is a major molecular constituent of Birbeck granules. We studied the emergence of Langerin expression in LC in epidermal sheets and cell suspensions during ontogeny. Langerin appears later than MHC II expression. Intracellular Langerin expression becomes apparent 2-3 d after birth. Only 10 days after birth all LC co-express Langerin. The intensity of Langerin expression reaches adult levels by 3 wk after birth. Early Langerin expression appears to correlate at least in part with the physical presence of Birbeck granules.

Identification of an indispensable role for tyrosine kinase 2 in CTL-mediated tumor surveillance.

We showed previously that Tyk2(-/-) natural killer cells lack the ability to lyse leukemic cells. As a consequence, the animals are leukemia prone. Here, we show that the impaired tumor surveillance extends to T cells. Challenging Tyk2(-/-) mice with EL4 thymoma significantly decreased disease latency. The crucial role of Tyk2 for CTL function was further characterized using the ovalbumin-expressing EG7 cells. Tyk2(-/-) OT-1 mice developed EG7-induced tumors significantly faster compared with wild-type (wt) controls. In vivo assays confirmed the defect in CD8(+) cytotoxicity on Tyk2 deficiency and clearly linked it to type I IFN signaling. An impaired CTL activity was only observed in IFNAR1(-/-) animals but not on IFNgamma or IL12p35 deficiency. Accordingly, EG7-induced tumors grew faster in IFNAR1(-/-) and Tyk2(-/-) but not in IFNgamma(-/-) or IL12p35(-/-) mice. Adoptive transfer experiments defined a key role of Tyk2 in CTL-mediated tumor surveillance. In contrast to wt OT-1 cells, Tyk2(-/-) OT-1 T cells were incapable of controlling EG7-induced tumor growth.