{"title":"Nucleic Acid Therapy for the Skin.","authors":"Andreas C Chai,Daniel J Siegwart,Richard C Wang","doi":"10.1016/j.jid.2024.07.029","DOIUrl":"https://doi.org/10.1016/j.jid.2024.07.029","url":null,"abstract":"Advances in sequencing technologies have facilitated the identification of the genes and mechanisms for many inherited skin diseases. Although targeted nucleic acid therapeutics for diseases in other organs have begun to be deployed in patients, the goal of precise therapeutics for skin diseases has not yet been realized. First, we review the current and emerging nucleic acid-based gene-editing and delivery modalities. Next, current and emerging viral and nanoparticle vehicles for the delivery of gene therapies are reviewed. Finally, specific skin diseases that could benefit optimally from nucleic acid therapies are highlighted. By adopting the latest technologies and addressing specific barriers related to skin biology, nucleic acid therapeutics have the potential to revolutionize treatments for patients with skin disease.","PeriodicalId":16311,"journal":{"name":"Journal of Investigative Dermatology","volume":"115 1","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Connexin Hemichannel Inhibition and Human Genodermatoses.","authors":"Fabio Mammano,Amy S Paller,Thomas W White","doi":"10.1016/j.jid.2024.08.003","DOIUrl":"https://doi.org/10.1016/j.jid.2024.08.003","url":null,"abstract":"Pathogenic variants in genes encoding connexins that cause skin diseases, such as keratitis-ichthyosis-deafness (KID) syndrome and hidrotic ectodermal dysplasia (HED) or Clouston syndrome, display increased hemichannel activity. Mechanistic insights derived from biophysical studies of the variant connexins support the hypothesis that inhibition of the acquired hemichannel activity could alleviate epidermal pathology. Use of pharmacological blockers and engineered mAbs in mouse models of HED and KID confirm that hemichannel inhibition is a promising target for new therapeutic approaches to KID and HED. Insights from this work could apply to other connexin-based genetic skin diseases in which hemichannel activity is elevated.","PeriodicalId":16311,"journal":{"name":"Journal of Investigative Dermatology","volume":"7 1","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inhibition of adipocyte-derived fatty-acid-binding protein 4 reduces adipocyte inflammation, improves angiogenesis, and facilitates wound healing in metabolic dysfunctions.","authors":"Yen-Wen Wu,Jaw-Wen Chen,Hao-Yuan Tsai,Jih-Hsin Huang,Chia-Chi Chang,Ting-Ting Chang","doi":"10.1016/j.jid.2024.08.017","DOIUrl":"https://doi.org/10.1016/j.jid.2024.08.017","url":null,"abstract":"Dermal white adipose tissue may participate in the wound healing process. Obesity-mediated chronic low-grade inflammation impairs wound healing by suppressing vascularity. Given that fatty-acid-binding protein (FABP) 4 is upregulated in the skin tissue of obese animals, this study aimed to investigate the effects of FABP4 inhibition on wound healing in high-fat-diet (HFD)-induced metabolic dysfunction mice in vivo. The interaction between adipocyte-derived FABP4 and vascular endothelial cell function was also investigated. In HFD-induced metabolic dysfunction mice, FABP4 inhibition increased angiogenesis and facilitated wound healing with reduced wound inflammation. FABP4 inhibition not only attenuated systemic inflammation, decreased body weight, and reduced insulin resistance, but also improved the sizes of adipocytes and hypoxic conditions in dermal white adipose tissue. The in vitro hypoxia was used to induce adipocyte inflammation, and the supernatants from hypoxia-stimulated adipocytes impaired the function and angiogenetic capability of human dermal microvascular endothelial cells. Both of them were improved by FABP4 inhibition. Altogether, FABP4 inhibition reduced systemic and adipocyte inflammation, improved vascular endothelial cell function, and facilitated wound healing in metabolic dysfunctions. Given the complex involvement of wound healing, future studies may be required to validate FABP4 as a potential therapeutic target for wound repair in metabolic dysfunctions.","PeriodicalId":16311,"journal":{"name":"Journal of Investigative Dermatology","volume":"260-261 1","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142175331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marjorie Flahaut , Alexis Laurent , Carla V. Fuenteslópez , Zhanfeng Cui , Hua Ye , Corinne Scaletta , Nathalie Hirt-Burri , Lee Ann Applegate , Viorica Patrulea
{"title":"Reassessing Long-Term Cryopreservation Strategies for Improved Quality, Safety, and Clinical Use of Allogeneic Dermal Progenitor Cells","authors":"Marjorie Flahaut , Alexis Laurent , Carla V. Fuenteslópez , Zhanfeng Cui , Hua Ye , Corinne Scaletta , Nathalie Hirt-Burri , Lee Ann Applegate , Viorica Patrulea","doi":"10.1016/j.jid.2024.06.1285","DOIUrl":"10.1016/j.jid.2024.06.1285","url":null,"abstract":"<div><p>In regenerative medicine, ongoing advancements in cell culture techniques, including isolation, expansion, banking, and transport, are crucial for clinical success. Cryopreservation ensures off-the-freezer availability of living cells, enabling long-term storage and transport. Customizing cryopreservation techniques and cryoprotective agents (CPAs) for specific cell types is crucial for cell source quality, sustainability, safety, and therapeutic intervention efficiency. As regenerative medicine progresses, it becomes imperative that the scientific community and industry provide a comprehensive, cell-specific landscape of available and effective cryopreservation techniques, preventing trial-and-error approaches and unlocking the full potential of cell-based therapies. Open-sharing data could lead to safer, more efficient cell therapies and treatments. Two decades of dermal progenitor cell use for burn wound treatment and Good Manufacturing Practice–compliant technology transfers have highlighted the need for further cryopreservation optimization in manufacturing workflows. In this paper, we present experimental data assessing 5 different cryopreservation formulae for long-term storage of clinical-grade FE002 primary progenitor fibroblasts, emphasizing the crucial difference between DMSO-based and DMSO-free CPAs. Our findings suggest that CryoOx, a DMSO-free CPA, is a promising alternative yielding cell viability similar to that of established commercial CPAs. This research highlights the importance of secure, robust, and efficient cryopreservation techniques in cell banking for maximizing quality, ensuring patient safety, and advancing regenerative medicine.</p></div>","PeriodicalId":16311,"journal":{"name":"Journal of Investigative Dermatology","volume":"144 10","pages":"Pages 2125-2135"},"PeriodicalIF":5.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0022202X24018980/pdfft?md5=767719649077973ef2a295101353718d&pid=1-s2.0-S0022202X24018980-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Hungry Side of Skin","authors":"Shivang Parikh , Carmit Levy","doi":"10.1016/j.jid.2024.04.030","DOIUrl":"10.1016/j.jid.2024.04.030","url":null,"abstract":"","PeriodicalId":16311,"journal":{"name":"Journal of Investigative Dermatology","volume":"144 10","pages":"Pages 2117-2119"},"PeriodicalIF":5.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immune Landscape within Cutaneous Lesions of Human Bullous Pemphigoid","authors":"Kalpani de Silva , Jun Yan","doi":"10.1016/j.jid.2024.04.008","DOIUrl":"10.1016/j.jid.2024.04.008","url":null,"abstract":"","PeriodicalId":16311,"journal":{"name":"Journal of Investigative Dermatology","volume":"144 10","pages":"Pages 2111-2113"},"PeriodicalIF":5.7,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142038082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Childhood Obesity, Weight Change, and Pediatric Immune-Mediated Skin Diseases","authors":"Seong Rae Kim , Seong-Joon Koh , Hyunsun Park","doi":"10.1016/j.jid.2024.01.037","DOIUrl":"10.1016/j.jid.2024.01.037","url":null,"abstract":"<div><p>Whether childhood obesity or weight gain leads to the development of pediatric immune-mediated skin diseases remains unclear. We aimed to determine the associations between body mass index or body mass index changes and the development of 3 main immune-mediated skin diseases—alopecia areata, atopic dermatitis (AD), and psoriasis—by analyzing a longitudinal cohort of 2,161,900 Korean children from 2009 to 2020. The findings indicated that children who were obese had a higher risk of pediatric immune-mediated skin diseases than those with normal weight (<em>P</em> for trend < .01). An increase in body mass index was associated with a higher risk of AD, whereas a decrease in body mass index was correlated with a reduced risk of AD. Children who gained weight, transitioning from normal to overweight, exhibited a higher AD risk than those who maintained a normal weight (adjusted hazard ratio = 1.15, 95% confidence interval = 1.11–1.20). However, those who shifted from being overweight to achieving a normal weight (adjusted hazard ratio = 0.87, 95% confidence interval = 0.81–0.94) had a lower AD risk than children who were overweight who maintained their weight. In summary, early childhood obesity may increase the risk of pediatric immune-mediated skin diseases. Weight gain may increase AD risk, whereas weight loss may lower the risk.</p></div>","PeriodicalId":16311,"journal":{"name":"Journal of Investigative Dermatology","volume":"144 9","pages":"Pages 1975-1984.e10"},"PeriodicalIF":5.7,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142038080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}