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Platelet α-granules release growth factors (GFs) that promote healing and tissue regeneration by stimulating cell proliferation and differentiation. Platelet-rich plasma (PRP) prepared from autologous blood has shown to be beneficial in treating alopecia, however, clinical response can be inconsistent. Due to several fold enrichment of platelets secreting large quantities of GFs following PRP injections, variable GF secretion by platelets between patients may contribute to inconsistent clinical response.
ARHGAP29 is a Rho GTPase Activating Protein with a high affinity for the small GTPase RhoA. In endothelial cells, ARHGAP29 regulates tubulogenesis and endothelial barrier function. However, very little is know about the role of ARHGAP29 in keratinocytes. We previously demonstrated that ARHGAP29 was reduced in Irf6-deficient skin and keratinocytes. Beause IRF6 is required for keratinocyte migration, we hypothesize that ARHGAP29 also regulates keratinocyte migration. To test this hypothesis, we used CRISPR-Cas9 technology to generate keratinocyte cell lines possessing two mutant alleles for ARHGAP29.
Dermal white adipose tissue (dWAT) is key for multiple processes in the skin, ranging from immune response to hair growth. The generation of mature adipocytes in the skin relies on the proliferation and differentiation of adipocyte precursors (APCs). APCs can be identified by the expression of surface markers such as CD29, CD34, Sca1, and CD24, however the true extent of APC heterogeneity remains largely unknown. Using single-cell RNA sequencing (scRNA-seq) we reveal an unprecedented degree of heterogeneity in skin APCs.
Corneal wounds are a leading cause of blindness and therapeutic approaches that target early epithelial wound healing can minimize the risk of blindness. Preliminary studies of corneal wounds showed increased SFK activity at the wound edge. Therefore, we hypothesized that increased SFK activity may promote corneal epithelial wound healing in vitro and in vivo. Our data show that in vitro wound healing in primary human corneal epithelial cells (HCEC) is enhanced when SFK levels are increased by sodium orthovanadate (NaVO4).
Compression garments (CGs) such as bandages and stockings are critical in the management of a wide range of lower extremity conditions, particularly venous leg ulcers (VLUs). In order for CGs to deliver therapeutic benefit, the interface pressure between the fabric and the skin much typically reach at least 30 mmHg. However, this threshold value is highly sensitive to the type of CG material used, correct placement by a trained healthcare provider, body position, and leg volume changes. Currently, PicoPress® (Microlabitalia, Padua, Italy) is the gold-standard tool to measure interface pressure.
The clinical efficacy of Avène thermal spring water in atopic dermatitis, psoriasis or in reducing erythema post laser resurfacing have been shown by several studies. In addition to these soothing and immunomodulatory properties, in-vitro experiments have also demonstrated effects of Avène thermal spring water on stimulation of keratinocyte differentiation and improvement of membrane fluidity, suggesting a potential effect on skin barrier and repair. An investigation of the deep aquifer of the Avène thermal spring water pointed out a new microorganism as a potential source of these unique properties.
Platelet-rich Plasma (PRP) plays an important role on the tissue regeneration process. A new preparatioin method of PRP provides an filling injection product which was named Platelet-rich Plasma Gel (PRPG) and could provied synergic effects on skin elasticity, dermal remodeling and re-vascularization. The aim of this pilot study was to assess the clinical benefit of PRPG filling injection on the treatment of en coup de sabre scleroderma. Five patients who were diagnosed under the confirmation of histopathology, and assessed by ultrasonography.
Wound healing is a multi-step complex mechanism during which dermal angiogenesis is a critical factor. Human dermis has a complex architecture, divided into papillary and reticular dermis which are characterized by distinct extracellular matrix (ECM) and vasculature. Nowadays, the contribution of each subtype of fibroblasts in the generation of specific ECM and vasculature is poorly documented. The aim was to determine if papillary and reticular fibroblasts generate specific 3D microenvironments and then evaluate their impact on angiogenesis.
The epigenetic machinery regulates epidermal homeostasis and keratinocyte differentiation is normal skin, while epigenetic control of wound healing remains relatively underexplored. The HDAC1/2 and LSD1 enzymatic activities within the CoREST complex are commonly associated with silencing of gene expression. Corin is a synthetic hybrid agent derived from the HDAC inhibitor (MS-275) and LSD1 inhibitor. In this study, using in vivo mouse tail wound healing model, we found that HDAC1 and LSD1 expression levels in epidermal keratinocytes show dynamic changes after injury compared to uninjured skin.
Chronic foot ulcers are a major cause of morbidity and mortality in 25% of individuals with type 2 diabetes (T2D). Our laboratory has previously shown increased expression of sphingolipid GM3 and GM3 synthase (GM3S) in human diabetic foot skin. Preventing increases in GM3 in a diet-induced mouse diabetic model or in high glucose-treated 2D keratinocyte cultures improved wound healing and scratch wound closure, respectively. To further test the role of increases in GM3/GM3S on wound healing in human T2D, a diabetic 3D human skin equivalent (HSE) model using diabetic foot ulcer fibroblasts (DFUFs) and normal keratinocytes was generated.
Antiviral proteins (AVPs) including the oligoadenylate-synthase (OAS) and Interferon induced transmembrane protein (IFITM) families have protective roles within the innate immune system. However, little is known about their regulation in skin. BMAL1 and CLOCK, regulators of the circadian rhythm, have known importance in a number of immune functions. We hypothesized that the circadian clock may regulate cutaneous AVP expression. We demonstrate that murine skin displays homeostatic oscillations of AVP expression through the day, and that AVPs exhibit modest rhythmic expression in primary human keratinocytes post-circadian synchronization using serum starvation or dexamethasone shock with a periodicity of 20 to 24 hours.
Bacterial biofilms are a major factor in delayed wound healing. Many staphylococcal species can form biofilms that have the potential to harm the host. DNA sequencing and qPCR of 16S RNA from bacteria isolated from human hair follicles by laser capture microdissection has shown that Staphylococci are highly abundant in the normal human follicles and co-exist with C. acnes. However, despite the high density of Staphylococci in follicles, biofilms seldom occur on healthy skin. We hypothesized that interactions between species in the commensal skin microbiome may regulate biofilm formation.
Heterotypic spheroids are used to study mesenchymal-epithelial interactions important for skin development and regeneration. In order to investigate the behavior and interaction of human hair follicle dermal papilla cells (DPC) and keratinocytes during in vitro three-dimensional (3D) co-culture, we labeled DPC and keratinocytes with two different fluorescent cell tracking dyes and prepared spheroids in DPC medium by hanging-drop technique. After incubation for 1 or 2 days, spheroids were live embedded in an agarose cylinder and image stacks were generated in multi-view mode from several angles using dual-sided LSFM.
Sites of specialized skin in humans, including the nipple-areola complex exhibit minimal scaring after wounding. The distinct epidermal and dermal features of these skin regions are induced and maintained by signaling from local fibroblasts. In contrast, trunk fibroblasts induce scarring after wounding and this is mediated by a subpopulation of that express high levels of dipeptidyl peptidase IV (DPP4/CD26). Profiling of transcripts of adult fibroblasts from a murine model of ectopic nipple development based on keratin 14 promoter driven parathyroid-related protein (KrP) transgene, identified increased levels of ovarian hormone receptors and matrix production, but decreased DPP4 and TGFB1 levels.
Scarring is a common sequelae of inflammatory acne vulgaris caused by the gram-positive bacterium, Cutibacterium acnes (C. acnes). Aberrant extracellular matrix remodeling seen in scarring may be due to upregulated activity of matrix metalloproteinases (MMPs) in the inflammatory response, resulting in loss of collagen deposition, increased tissue destruction, and imperfect repair during the wound healing process. C. acnes was shown previously to induce MMP-1 (collagenase) and MMP-9 (gelatinase) expression.
Background: Wound healing involve the migration of fibroblasts. The microenvironment of fibroblast migration is not beneficial for the survival of most pathogens due to lack of oxygen. However, for T. pallidum, the hypoxic environment is relatively suitable for survival. Ulceration lesion chancre, the early stage of syphilis, can heal spontaneously within a few weeks without treatment. The specific mechanism underlying this process is still unknown. Objective: Tp0136 is one of a few proteins produced by T.
Non-healing skin wounds are common and represent major medical, economic and social problems worldwide. Currently, there is a paucity of effective therapy for skin wounds. We have shown previously in several murine skin wound models that recombinant human type VII collagen (rhC7) dramatically accelerates wound closure and inhibits scarring. Murine skin wounds, however, heal much differently than human skin wounds. Therefore, in this study, we evaluated the effect of topical rhC7 on pigskin wounds.
Current tissue engineered skin fails to meet the need for skin replacement in full-thickness wounds. Bioprinting technology allows for fabrication of full-thickness skin with multiple cell types organized into biomimetic layers in vitro. The purpose of this study is to determine if bioprinted skin will integrate, form an epidermal barrier, and vascularize when implanted into full-thickness wounds on mice. Cells were isolated from human skin, expanded in vitro, suspended in a fibrinogen bioink, bioprinted to form a biomimetic tri-layer skin construct, and implanted onto 2.5 x 2.5cm full-thickness excisional wounds on mice.
Hippo signaling pathway is important for regulating cell growth, proliferation and organ development. It functions through the Yes-associated protein 1 (YAP1), which acts with the TEAD family transcription factors to regulate essential genes for proliferation and cell growth. However, it is not known whether TEAD (1-4) genes play redundant or non-redundant role in the human epidermal tissue development. We knocked down each individual TEAD and in combinations in human keratinocytes and found that only double knockdown of TEAD1 and TEAD3 resulted in a significant decrease of CTGF and AXL mRNAs as well as other critical self-renewal and proliferation genes (BIRC5, FGFBP1, CCNA2, MYC, CDK1, CYR61).
Impaired wound healing in irradiated tissue is a significant clinical problem which may be improved by stromal vascular fraction (SVF) containing pre-adipocytes. We studied the characteristics of dermal fibroblasts (DF)s derived from human breast skin exposed to radiotherapy to investigate challenges presented by irradiation prior to reconstruction, and whether the pre-adipocyte secretome has potential therapeutic benefit. Tissue collected from breast reduction (Ctrl), or reconstruction following 40 Gy hypofractionated radiotherapy (IR) was processed for histology, and isolation of primary DF and SVF cultures.