Navitoclax (ABT-263) Rejuvenates Human Skin by Eliminating Senescent Dermal Fibroblasts in a Mouse/Human Chimeric Model.

Chronic senescence, such as aging, contributes to age-related tissue dysfunction and disease development. The accumulation of senescent fibroblasts and the senescence-associated secretory phenotype is particularly implicated in this process. Removal of senescent cells has been reported to prevent tissue dysfunction and to extend the life span during aging. ABT-263 (navitoclax), which inhibits antiapoptotic proteins, is a leading antiaging drug; however, its role in human skin aging is unclear. This study aimed to determine the rejuvenating effects of ABT-263 on aging skin using a human skin graft mouse model. We assessed the viability of ABT-263-treated skin fibroblasts after inducing senescence. Aged human skin was transplanted under the back skin of nude mice and injected intraperitoneally with the drug or control. Analysis of the skin specimens revealed that ABT-263 induced selective elimination of senescent dermal fibroblasts. Senescent human skin treated with ABT-263 exhibited a decrease in the number of senescent cells and in the expression of aging-related secretory phenotype molecules, such as matrix metalloproteinases and interleukins and an increase in collagen density. Our results indicate that selective removal of senescent skin cells with ABT-263 can improve the aging phenotype of human skin without side effects. ABT-263 is, thus, a novel potential therapeutic agent for skin aging.

Glutaminase inhibitors rejuvenate human skin via clearance of senescent cells: a study using a mouse/human chimeric model.

Skin aging caused by various endogenous and exogenous factors results in structural and functional changes to skin components. However, the role of senescent cells in skin aging has not been clarified. To elucidate the function of senescent cells in skin aging, we evaluated the effects of the glutaminase inhibitor BPTES (bis-2-(5-phenylacetamido-1, 3, 4-thiadiazol-2-yl)ethyl sulfide) on human senescent dermal fibroblasts and aged human skin. Here, primary human dermal fibroblasts (HDFs) were induced to senescence by long-term passaging, ionizing radiation, and treatment with doxorubicin, an anticancer drug. Cell viability of HDFs was assessed after BPTES treatment. A mouse/human chimeric model was created by subcutaneously transplanting whole skin grafts from aged humans into nude mice. The model was treated intraperitoneally with BPTES or vehicle for 30 days. Skin samples were collected and subjected to reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting, and histological analysis. BPTES selectively eliminated senescent dermal fibroblasts regardless of the method used to induce senescence; aged human skin grafts treated with BPTES exhibited increased collagen density, increased cell proliferation in the dermis, and decreased aging-related secretory phenotypes, such as matrix metalloprotease and interleukin. These effects were maintained in the grafts 1 month after termination of the treatment. In conclusion, selective removal of senescent dermal fibroblasts can improve the skin aging phenotype, indicating that BPTES may be an effective novel therapeutic agent for skin aging.

Skin Wound Healing of the Adult Newt, Cynops pyrrhogaster: A Unique Re-Epithelialization and Scarless Model.

In surgical and cosmetic studies, scarless regeneration is an ideal method to heal skin wounds. To study the technologies that enable scarless skin wound healing in medicine, animal models are useful. However, four-limbed vertebrates, including humans, generally lose their competency of scarless regeneration as they transit to their terrestrial life-stages through metamorphosis, hatching or birth. Therefore, animals that serve as a model for postnatal humans must be an exception to this rule, such as the newt. Here, we evaluated the adult newt in detail for the first time. Using a Japanese fire-bellied newt, Cynops pyrrhogaster, we excised the full-thickness skin at various locations on the body, and surveyed their re-epithelialization, granulation or dermal fibrosis, and recovery of texture and appendages as well as color (hue, tone and pattern) for more than two years. We found that the skin of adult newts eventually regenerated exceptionally well through unique processes of re-epithelialization and the absence of fibrotic scar formation, except for the dorsal-lateral to ventral skin whose unique color patterns never recovered. Color pattern is species-specific. Consequently, the adult C. pyrrhogaster provides an ideal model system for studies aimed at perfect skin wound healing and regeneration in postnatal humans.

Clinical Analysis of Cultured Epidermal Autograft (JACE) Transplantation for Giant Congenital Melanocytic Nevus.

BACKGROUND: Cultured epidermal transplantation (JACE) is performed for giant congenital melanocytic nevus (GCMN), but there are few reports on its postoperative course and surgical content or indications. We aimed to investigate the postoperative course of GCMN patients undergoing cultured epidermal autograft transplantation and compare the outcomes between 2 nevus tissue resection methods. METHODS: Twelve GCMN patients aged 0 months to 8 years and 9 months were included in this single-center case series study. Cultured epidermal autograft transplantation was performed at 19 sites of the patients' extremities and trunks, after excision of the nevus either by using an electric dermatome, which we initially used in 2017, or by curettage with a sharp spoon and use of a hydrosurgery system (Versajet), which we started performing in 2018. Univariate and multivariate analyses were performed for factors associated with postoperative hypertrophic scar formation. RESULTS: In all cases, >90% of the grafts survived, and the dark brown color of the nevus was reduced. Average postoperative observation period was 16.5 months. Hypertrophic scar formation was observed postoperatively at 9 wound sites out of the 12 sites with GCMN removed with a dermatome and at only 1 site with GCMN removed by curettage with use of a hydrosurgery system. In the univariate and multivariate analyses, hypertrophic scar formation was associated with age at surgery. CONCLUSION: In cultured epidermal autograft transplantation for GCMN, nevus tissue removal at an early age by curettage with use of a hydrosurgery system can provide good results while reducing complications, including recurrence and hypertrophic scar formation.

A Giant Osteoma of the Ethmoid Sinus.

Osteomas are slow-growing, benign bony tumors. Most are asymptomatic. Paranasal sinus osteoma in the pediatric population is rare; hence, there are few reports of symptomatic osteomas. The authors report the case of a giant ethmoid sinus osteoma in an 11-year-old girl who presented with diplopia and proptosis. Total excision and reconstruction of the medial orbital wall were performed via a coronal approach. The postoperative period was uneventful, the child's vision improved, and a good cosmetic result was obtained.