Cell Therapy and the Skin: Great Potential but in Need of Optimization.

Cell therapy is rapidly growing owing to its therapeutic potential for diseases with currently poor outcomes. Cell therapy encompasses both nonengineered and engineered cells and possesses unique abilities such as sense-and-respond functions and long-term engraftment for persistent curative potential. Cell therapy capabilities have expanded to address a wide spectrum of diseases, and our review is focused on dermatological applications.

The use of ectopic volar fibroblasts to modify skin identity.

Skin identity is controlled by intrinsic features of the epidermis and dermis and their interactions. Modifying skin identity has clinical potential, such as the conversion of residual limb and stump (nonvolar) skin of amputees to pressure-responsive palmoplantar (volar) skin to enhance prosthesis use and minimize skin breakdown. Greater keratin 9 () expression, higher epidermal thickness, keratinocyte cytoplasmic size, collagen length, and elastin are markers of volar skin and likely contribute to volar skin resiliency.

Commensal microbe regulation of skin cells in disease.

Human skin is the host to various commensal microbes that constitute a substantial microbial community. The reciprocal communication between these microbial inhabitants and host cells upholds both the morphological and functional attributes of the skin layers, contributing indispensably to microenvironmental and tissue homeostasis. Thus, disruption of the skin barrier or imbalances in the microbial communities can exert profound effects on the behavior of host cells.

Testing the Reliability of Optical Coherence Tomography to Measure Epidermal Thickness and Distinguish Volar and Nonvolar Skin.

In persons with limb loss, prosthetic devices cause skin breakdown, largely because residual limb skin (nonvolar) is not intended to bear weight such as palmoplantar (volar) skin. Before evaluation of treatment efficacy to improve skin resiliency, efforts are needed to establish normative data and assess outcome metric reliability. The purpose of this study was to use optical coherence tomography to (i) characterize volar and nonvolar skin epidermal thickness and (ii) examine the reliability of optical coherence tomography.

Positive correlation of hidradenitis suppurativa and ultra-processed foods consumption.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition whose pathogenesis is not well established. An association between HS and obesity is suggested but few studies explore specific dietary drivers. Non-Hispanic Blacks have the highest HS prevalence and obesity rates as well as the highest UPFs consumption rates, as opposed to Hispanics who have the lowest prevalence of HS despite having the second highest obesity rates in the US.

Implementing a mailed stool sample screening program in clinics providing care for an underserved Hispanic population.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths in Hispanics in the US. Despite this, Hispanics are being screened for CRC at a much lower rate than their non-Hispanic white counterparts. Implementing mailed fecal immunochemical tests (FITs) is a cost-effective intervention for increasing CRC screening rates in vulnerable populations, such as Hispanic populations in border metroplexes.

Neutrophil-intrinsic TNF receptor signaling orchestrates host defense against .

is the leading cause of skin and soft tissue infections and is a major health burden due to the emergence of antibiotic-resistant strains. To address the unmet need of alternative treatments to antibiotics, a better understanding of the protective immune mechanisms against skin infection is warranted. Here, we report that tumor necrosis factor (TNF) promoted protection against in the skin, which was mediated by bone marrow-derived immune cells.

N6-methyladenosine RNA Methylation Correlates with Immune Microenvironment and Immunotherapy Response of Melanoma.

RNA methylation normally inhibits the self-recognition and immunogenicity of RNA. As such, it is likely an important inhibitor of cancer immune recognition in the tumor microenvironment, but how N6-methyladenosine (m6A) affects prognosis and treatment response remains unknown. In eight independent melanoma cohorts (1,564 patients), the modification patterns of 21 m6A gene signatures were systematically correlated with the immune cell infiltration of melanoma tumor microenvironment.

Topical SCD-153, a 4-methyl itaconate prodrug, for the treatment of alopecia areata.

Alopecia areata is a chronic hair loss disorder that involves autoimmune disruption of hair follicles by CD8  T cells. Most patients present with patchy hair loss on the scalp that improves spontaneously or with topical and intralesional steroids, topical minoxidil, or topical immunotherapy. However, recurrence of hair loss is common, and patients with extensive disease may require treatment with oral corticosteroids or oral Janus kinase (JAK) inhibitors, both of which may cause systemic toxicities with long-term use.

Commensal microbiome promotes hair follicle regeneration by inducing keratinocyte HIF-1α signaling and glutamine metabolism.

Tissue injury induces metabolic changes in stem cells, which likely modulate regeneration. Using a model of organ regeneration called wound-induced hair follicle neogenesis (WIHN), we identified skin-resident bacteria as key modulators of keratinocyte metabolism, demonstrating a positive correlation between bacterial load, glutamine metabolism, and regeneration. Specifically, through comprehensive multiomic analysis and single-cell RNA sequencing in murine skin, we show that bacterially induced hypoxia drives increased glutamine metabolism in keratinocytes with attendant enhancement of skin and hair follicle regeneration.

Wound-Induced Hair Neogenesis Model.

Skin wounds in adult mammals typically heal with a fibrotic scar and fail to restore ectodermal appendages, such as hair follicles or adipose tissue. Intriguingly, new hair follicles regenerate in the center of large full-thickness wounds of mice in a process called wound-induced hair neogenesis (WIHN). WIHN is followed by neogenesis of dermal adipose tissue.

Association of Early Clinical Response to Laser Rejuvenation of Photoaged Skin with Increased Lipid Metabolism and Restoration of Skin Barrier Function.

Laser resurfacing treatments for photoaged skin have improved dramatically over the past decades, but few studies have examined the molecular mechanisms underlying differences in clinical response. Seventeen white female participants with moderate-to-severe photoaging received nonablative fractional laser treatment on the face and forearm once monthly for 6 months. Biopsies for microarray analysis were performed at baseline and 7 days after facial treatment and at baseline and 1, 7, 14, and 29 days after forearm treatment in each participant, resulting in 119 total samples.

Keratinocyte-derived defensins activate neutrophil-specific receptors Mrgpra2a/b to prevent skin dysbiosis and bacterial infection.

Healthy skin maintains a diverse microbiome and a potent immune system to fight off infections. Here, we discovered that the epithelial-cell-derived antimicrobial peptides defensins activated orphan G-protein-coupled receptors (GPCRs) Mrgpra2a/b on neutrophils. This signaling axis was required for effective neutrophil-mediated skin immunity and microbiome homeostasis.

Clinical and molecular change induced by repeated low-dose visible light exposure in both light-skinned and dark-skinned individuals.

Background: Visible light (VL) is known to induce pigmentation in dark-skinned individuals and immediate erythema in light-skinned individuals. However, the effects of accumulated low-dose VL exposure across skin types are not well established.

Methods: Thirty-one healthy subjects with light (Fitzpatrick skin types [FST] I-II, n = 13) and dark (FST V-VI, n = 18) skin types were enrolled.

Toward Understanding Wound Immunology for High-Fidelity Skin Regeneration.

Effective tissue repair is vital for the survival of organisms. Yet, how the immune system coordinates with tissue stem cells (SCs) to effect postnatal tissue restoration remains elusive. This review presents current knowledge surrounding wound-induced SC and immune signaling that favors tissue repair, including wound healing and regeneration.

Mechanical tension mobilizes Lgr6 epidermal stem cells to drive skin growth.

Uniquely among mammalian organs, skin is capable of marked size change in adults, yet the mechanisms underlying this notable capacity are unclear. Here, we use a system of controlled tissue expansion in mice to uncover cellular and molecular determinants of skin growth. Through machine learning-guided three-dimensional tissue reconstruction, we capture morphometric changes in growing skin.

A data management infrastructure for the integration of imaging and omics data in life sciences.

Background: As technical developments in omics and biomedical imaging increase the throughput of data generation in life sciences, the need for information systems capable of managing heterogeneous digital assets is increasing. In particular, systems supporting the findability, accessibility, interoperability, and reusability (FAIR) principles of scientific data management.

Results: We propose a Service Oriented Architecture approach for integrated management and analysis of multi-omics and biomedical imaging data.