Senescence-associated secretory phenotypes in mesenchymal cells contribute to cytotoxic immune response in oral lichen planus.

Oral lichen planus is a chronic inflammatory condition that adversely affects the oral mucosa; however, its etiology remains elusive. Consequently, therapeutic interventions for oral lichen planus are limited to symptomatic management. This study provides evidence of the accumulation of senescent mesenchymal cells, CD8 + T cells, and natural killer cells in patients with oral lichen planus. We profiled the patients' tissues using the National Center for Biotechnology Information Gene Expression Omnibus database and found that senescence-related genes were upregulated in these tissues by gene set enrichment analysis. Immunohistochemical analysis showed increased senescent mesenchymal cells in the subepithelial layer of patients with oral lichen planus. Single-cell RNA-seq data retrieved from the Gene Expression Omnibus database of patients with oral lichen planus revealed that mesenchymal cells were marked by the upregulation of senescence-related genes. Cell-cell communication analysis using CellChat showed that senescent mesenchymal cells significantly influenced CD8 + T cells and natural killer cells via CXCL12-CXCR4 signaling, which is known to activate and recruit CD8 + T cells and NK cells. Finally, in vitro assays demonstrated that the secretion of senescence-associated factors from mesenchymal cells stimulated the activation of T cells and natural killer cells and promoted epithelial cell senescence and cytotoxicity. These findings suggest that the accumulation of mesenchymal cells with senescence-associated secretory phenotype may be a key driver of oral lichen planus pathogenesis.

Cellular senescence and wound healing in aged and diabetic skin.

Cellular senescence is a biological mechanism that prevents abnormal cell proliferation during tissue repair, and it is often accompanied by the secretion of various factors, such as cytokines and chemokines, known as the senescence-associated secretory phenotype (SASP). SASP-mediated cell-to-cell communication promotes tissue repair, regeneration, and development. However, senescent cells can accumulate abnormally at injury sites, leading to excessive inflammation, tissue dysfunction, and intractable wounds. The effects of cellular senescence on skin wound healing can be both beneficial and detrimental, depending on the condition. Here, we reviewed the functional differences in cellular senescence that emerge during wound healing, chronic inflammation, and skin aging. We also review the latest mechanisms of wound healing in the epidermis, dermis, and subcutaneous fat, with a focus on cellular senescence, chronic inflammation, and tissue regeneration. Finally, we discuss the potential clinical applications of promoting and inhibiting cellular senescence to maximize benefits and minimize detrimental effects.

Altered regulation of mesenchymal cell senescence in adipose tissue promotes pathological changes associated with diabetic wound healing.

Pathologic diabetic wound healing is caused by sequential and progressive deterioration of hemostasis, inflammation, proliferation, and resolution/remodeling. Cellular senescence promotes wound healing; however, diabetic wounds exhibit low levels of senescent factors and accumulate senescent cells, which impair the healing process. Here we show that the number of p15INK4B + PDGFRα + senescent mesenchymal cells in adipose tissue increases transiently during early phases of wound healing in both non-diabetic mice and humans. Transplantation of adipose tissue from diabetic mice into non-diabetic mice results in impaired wound healing and an altered cellular senescence-associated secretory phenotype (SASP), suggesting that insufficient induction of adipose tissue senescence after injury is a pathological mechanism of diabetic wound healing. These results provide insight into how regulation of senescence in adipose tissue contributes to wound healing and could constitute a basis for developing therapeutic treatment for wound healing impairment in diabetes.

Intrathecal Injection of Mesenchymal Stromal Cell Cultured on 3D Fiber Ameliorates Multiple Organ Damage in Murine Lupus.

Up to 60% of patients with systemic lupus erythematosus (SLE) experience autonomic symptom. Sympathetic nervous system damage can cause dysfunction of the bone marrow that activates inflammatory cells, potentially causing multiple organ damage. We hypothesized that sympathetic nervous system damage would induce bone marrow dysfunction with multiple organ damage in SLE, and that multiple organ damage could be improved by therapy targeting the nervous system. Here, we showed that damage to autonomic nerves and Schwann cells occurred in the bone marrow and central nervous system of SLE model mice. A neurotoxic drug increased mortality and induced severe neuropathy and multiple organ damage, while a neuroprotective drug prevented multiple organ damage. The administration of bone marrow-derived mesenchymal stromal cells (BMSCs) cultured on a 3-dimensional fiber scaffold improved bone marrow neuropathy, skin lesions, kidney function, and mortality. Our results reveal that bone marrow neuropathy influence multiple organ damage associated with SLE, and improvement of bone marrow neuropathy by intrathecal injection of BMSC may be a target for SLE multiple-organ damage.

Full-thickness total upper eyelid reconstruction with a lid switch flap and a reverse superficial temporal artery flap.

BACKGROUND: Reconstruction of the upper eyelid with the same eyelid tissue is desirable because of the ability to achieve eye opening/closing and corneal protection, and a lid switch flap is a useful method. For total defects, almost all of the tissues of the lower eyelid should be used; however, the reconstruction of the lower eyelid donor site has often been undervalued. Reconstruction with an insufficient amount of soft tissue often results in complications such as lagophthalmos and ectropion. Here, we report our method of management of total upper eyelid defects and secondary reconstruction of the lower eyelid donor site. METHOD: A lid switch flap is designed on the lower eyelid as the first operation. As important points, the height of the flap of the anterior lamina should be the same but the conjunctiva as the posterior lamina should be harvested up to the conjunctival fornix to obtain sufficient tissue. After switching the flap, the lower eyelid donor site is reconstructed with sufficient tissue: cheek mucosa, conchal cartilage, and a reverse superficial temporal artery flap as a three-layered structure. RESULTS: Three patients were treated using our method, and we achieved favorable results with a sufficient amount of soft tissue for the reconstruction of the lower eyelid. CONCLUSION: Reconstruction of the upper eyelid with sufficient tissue from the lower eyelid is important for eyelid function.

New technical method to correct secondary vermilion deformities with cleft lip.

Various techniques for correcting whistling deformities that occurred after primary surgery for cleft lip have been reported. These techniques are mainly intended to correct the lack of volume of the red lip. However, irregularity of the dry-wet lip junction (mucocutaneous junction) in the red lip has rarely been mentioned. If the wet lip is located in an exposed area, not only is the aesthetic appearance poor but also uncomfortable complications such as a crusted or bleeding lip repeatedly occur under a dry condition. A new technique for correcting the irregular line of the dry-wet lip junction is described in this report. The technique is simple. After removal of the exposed wet lip, flaps are designed on both dry lip sides of the defect as M-W-M plasty and are transposed toward the defect. The dog-ears are small; the scar is inconspicuous because it is incorporated with the wrinkle line, and scar contracture is prevented. In addition, more soft tissues may be included to correct a mild whistling deformity.

Subcutaneous pedicle V-Y flap for release of incomplete congenital syndactyly.

BACKGROUND: Various procedures for correction of congenital syndactyly of hand or foot have been described. For incomplete syndactyly, some of the reported techniques use only local flaps from surrounding tissues. A novel technique for the correction of incomplete syndactyly, using a dorsal triangular flap and two palmar small flaps, is described in this article. METHODS: A triangular flap is first marked on the affected web space. The size of the flap should be the same as the unaffected side or other web space. Then a straight line is marked from the proximal apex of the triangle to the level of the metacarpophalangeal (MP) joint. After full skin incision, minimal peripheral undermining is done, and the triangular flap is transposed proximally, as in the Y-V advancement procedure, and sutured. Then two incisions are made from the distal part of the flap, transposing small flaps as in the five-flap method, and closed primarily. RESULTS: We treated ten cases of congenital syndactyly of the hand or foot. We were able to correct a good web space without skin grafting in all cases. CONCLUSION: The design for our technique is simple, and the technique can be performed easily. The operation can be performed in a short time, the blood supply of the flap is preserved, the flap has a wide range of motion, and a deep and smooth dorsal slope is produced. This technique is an attractive alternative to previously reported methods for syndactyly correction.

Correction of lobule-type microtia: I. The first stage of costal cartilage grafting.

BACKGROUND: Recently, auriculoplasty with costal cartilage grafting has been successfully used for correcting microtia and creating a clearly refined contour and a natural appearance of the ear. However, several important problems remain unsolved in these techniques. The authors describe an improved technique for harvesting costal cartilage with minimal morbidity and a new procedure for fabricating a cartilage frame that ensures a refined shape and rigid structure of the constructed ear. METHODS: Costal cartilage is harvested directly with a chisel. This technique enables some of the cartilage at the chest wall to remain intact. The base frame is fabricated by two cartilage blocks partly overlapped on the area of the antihelix. The thickness in the overlapping area emphasizes the contour between the antihelix and the helical crus. To prevent absorption of the cartilage, helical and antihelical parts are created using the outer rigid layer of the harvested cartilage and are covered as much as possible by perichondrium. RESULTS: A total of 137 ears in 121 patients were corrected with the authors' technique and followed up for at least 3 years. Almost all of the patients could walk within 2 days after the operation. The structure and contour of the constructed ear were well maintained. CONCLUSIONS: Attention should be given not only to successful outcomes of construction of the ear but also to minimal morbidity for the patients. Our technique made it possible to construct a cosmetically refined ear that could be maintained for a long period and minimize the pain and deformity of the donor's chest.