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Despite great scientific and clinical successes, few tissue engineering products have so far made their way to the industrial and commercial phase, depriving patients to benefit from innovative treatments. Producing advanced therapy medicinal products remains a cumbersome process with costs, reproducibility and scalability issues. Automation of production processes should be key to achieve quality controlled and repeatable biomanufacturing. Poietis develops biomanufacturing solutions based on bioprinting technologies for the design and the production of tissues, like the full thickness skin model Poieskin®.
Hibiscus abelmoschus seed extract is used in anti-ageing cosmetics and improves both the firmness of skin and reduces the appearance of wrinkles. Whilst it promotes collagen production, less is known about its wider impact upon the remodelling of the dermal extracellular matrix (ECM). In this study we investigated its effects upon the expression and deposition of key ECM biomarkers. A formulation containing the botanical derivative was prepared as an oil in water gel cream and applied to photoaged extensor forearm of healthy individuals (n=9; aged 61-79).
Skin is the largest organ of the body involved in self-protection against external damages. Epidermis, the upper layer of the skin is mainly composed of keratinocytes organized to form a physical barrier at the interface of the environment. Some of diseases associated to genetic mutations or not could weaken this protection and lead to the disruption of skin integrity. Cell therapy approaches using adult keratinocytes are currently envisaged however these cells present limited proliferative capacities and variability in genetic background.
Eruptive sebaceous hyperplasia has been reported to appear in male organ transplant patients treated with an immunosuppressive drug, cyclosporine. In addition, it has been reported that there is no onset of eruptive sebaceous hyperplasia on other immunosuppressive medications with azathioprine or prednisolone. Therefore, cyclosporine may directly influence sebaceous gland functions such as sebocyte lipogenesis and proliferation. In the present study, when hamster sebocytes were treated with cyclosporine, oil-red O staining revealed that intracellular lipid droplet formation was augmented in a dose-dependent manner.
We have previously shown that cannabidiol (CBD) exerts complex anti-acne effects in vitro, and in vivo efficiency of topically administered CBD in moderate to severe acne is currently being assessed in a phase II clinical trial (ID at clinicaltrials.gov: NCT03573518). We have also demonstrated that anti-acne effects of CBD were at least in part mediated by the activation/up-regulation of tribbles homolog 3 (TRIB3). Thus, here, we aimed to assess the effects of the plant-derived TRIB3-activator honokiol (HNK) on human SZ95 sebocytes.
IIn humans, perspiration is essential for skin homeostasis. Sweat consists of metabolites, antibiotic peptides, and electrolytes; and it contributes to body temperature regulation, immune defense, and moisture retention. Acquired idiopathic generalized anhidrosis (AIGA) is an intractable disease that causes skin dryness and may result in fatal heatstroke. Symptoms related to AIGA impair patient quality of life scores; however, there are currently few promising treatment strategies. The etiology of AIGA remains obscure; therefore, further study is greatly warranted to better establish disease therapy.
Hidradenitis suppurativa/acne inversa (HS) is a chronic, recurrent skin disease of the hair follicle. It manifests with painful, deeply localized, inflammatory skin lesions that occur in apocrine gland-rich areas of the skin, most commonly in the axillae and the inguinal and anogenital regions (Dessauer definition). The central pathogenic event in HS is believed to be the occlusion of the hair follicle leading to a perifollicular lymphohistiocytic inflammation. The purpose of this work was to develop a human HS model which could help to understand the pathophysiology of HS and to determine the action of therapeutic candidates.
Human scalp skin and hair follicles (HF) (most prominently at the level of the bulge) are densely innervated by sensory peripheral nerve fibers (NF) suggestingthat neuromediators released by cutaneous NFs impact on human epidermis and HF activities and vice versa. While imbalance of this complex bi-directional communication, associated e.g. with neurogenic skin inflammation, may contribute to the development of skin and hair disorders, it has not yet been possible to dissect these bi-directional interactions in a fully humanized re-innervated ex vivo model.
Epidermolysis Bullosa simplex (EBS) is a rare disease, characterized by blistering and erosion of the skin and mucous membrane where the separation occurs within the basal layer of the epidermis due to fragility of basal keratinocytes. This disease is mostly inherited in autosomal dominant fashion, mostly due to mutations affecting either keratin 5 (KRT5) or keratin 14 (KRT14) genes. Most of reported EBS human models come from patient immortalized cell lines which limit the study of pathological phenotypes.
The Sry-related high-mobility-group box (Sox) gene encodes a transcription factor family that plays crucial roles in the determination of cell fate and organogenesis. Sox13, a group D member of the Sox family, is expressed in various tissues such as brain, cartilage, hair, kidney, pancreas, liver, kidney and blood vessels. However, knowledge of the biological roles of Sox13 is largely limited. To examine the precise expression domains of Sox13 protein and its role in mouse development, we generated Sox13-LacZ-knock-in mice (Sox13LacZ/+), in which the Sox13 coding sequence was disrupted by an in-frame insertion of the b-galactosidase (LacZ) gene.
Syringotropic cell infiltration is recognized as histological hallmarks in autoimmne diseases, including lupus eythematosus (LE) and Sjögren syndrome (SjS). Previously, we implicated the existence of immune privilege (IP) in the human sweat gland (SG). In this study, we adopted in–depth digital histological image analyses in combination with human skin organ culture to dissect the role of SG IP collapse in syringotropic inflammation. The digital image analysis allows the quantification and statistical analyses of differential expression of IP molecules in immunohistochemically stained sections.
Androgenic alopecia affects hair follicles (HFs) from frontal and vertex area. Hair inductive properties of DPCs are lost in bi-dimentional (2D) culture. In a recent study three dimentional (3D) structure of cultured DPCs was able to recapitulate 22% of molecular signature of the intact dermal papilla. The aim of this study is to compare gene expression differences between DPCs from balding scalp and non balding scalp (occipital area) and their changes in 2D and 3D cultures. We investigated whether 3D structure of these immortalized cells and their co-culture with ASCs could increase the expression of hair inductivity markers.
In oncology, permanent chemotherapy-induced alopecia (pCIA) remains an unfulfilled clinical need. Irreversible hair loss may result from permanent damage of hair follicle bulge epithelial stem cells (HFeSCs), some of which may undergo epithelial-mesenchymal transition (EMT). To prove our hypothesis, we treated ex vivo full-length HFs with 4HC, a cyclophosphamide metabolite 4HC, which routinely induces reversible CIA and sometimes pCIA. PPARγ signaling is known to have a protective role in eSCs biology.
Human hair follicles (HF) engage in olfactory receptor (OR)-dependent chemosensation via OR2AT4 and continuous signaling is required for anagen maintenance ex vivo. OR2AT4 is expressed mainly in the suprabulbar outer root sheath (ORS) and selectively targeted by the synthetic sandalwood odorant (Sandalore®). Microarray analysis revealed that Sandalore® strongly up-regulates dermcidin (DCD) transcription in microdissected HFs ex vivo. DCD is an antimicrobial peptide with activity against S. aureus, S.
Human hair follicles (HFs) have a high demand for energy and biosynthesis precursors fulfilled mainly by aerobic glycolysis. HFs contain high levels of glycogen the main means by which glucose is stored in the body. In the liver lactate is converted to glucose and glycogen through gluconeogenesis via the Cori cycle. As the hair follicle is known to engage in aerobic glycolysis with the generation of lactate the aim of this study is to investigate both the role of glycogen in the hair follicle and whether the HF operates its own internal Cori cycle.
Skin is the largest organ of the body and the more exposed to free radicals produced by cellular metabolism, stress and present in our external environment. Consequently, those free radicals induce a premature skin aging and an increase of the risk of skin cancer. Supplementation with anti-oxidant molecules is effective to reduce the effect of oxidative stress. Among antioxidants, selenoproteins play a key role in antioxidant defense and in maintaining a reduced cellular environment. Selenium, essential for their activity, is an essential trace element that must be provided by diet or supplementation.
Since many years, we studied human pigmentation using a model of skin reconstruct on dead deepidermized dermis. These reconstructs were made with human primary cells obtained from human skin (control or pathological). Since this model has a short lifetime, we improved our technic of reconstruction to have efficient engraftment on immunodeficient mice in order to achieve long-term studies such as effect of chronic irradiation. Furthermore, dermal collagen-based matrices such as IntegraTM or Matriderm® were used as dermal substitute from many years in reconstructive surgery.
Vasculature cross-talking with epithelial stem cells is not understood in adult skin homeostasis. Skin vasculature undergoes dramatic remodeling during adult hair cycle. Specifically, a dermal horizontal plexus transiently neighbors the hair follicle stem cell activation zone during the quiescence phase of hair homeostasis (cycle). We showed that increased density of this plexus was induced by reciprocal mutations in the epithelium (Runx1) and endothelium (Alk1). This increase in vasculature correlates with prolonged quiescence of hair follicle stem cells and delayed entry into the hair growth phase, suggesting an inhibitory role of dense vasculature neighboring stem cells.
Noninvasive identification and evaluation of cultured stem cells and their proliferative capacity advance stem cell-based regenerative medicine. Here we provide a novel quantitative cell motion analysis that can identify human keratinocyte stem cells (holoclones) without any labeling. We trained a Single Shot MultiBox Detector (SSD) deep learning model by using a large number of phase-contrast images of cultured human epidermal keratinocytes. The SSD model successfully identified keratinocytes in the phase-contrast images.
Hair follicle (HF) cyclical growth is ruled by interactions between dermal papilla cells (DPC) and epidermal HF stem cells (HFSC). In androgenetic alopecia (AGA) androgens deregulate these interactions impairing HFSC differentiation. BMPs and WNTs maintain hair-inducing activity of DPC. We studied the role of BMPs on HFSC differentiation process to follicular linage, induced by DPC, and on its inhibition by androgens. The activity of alkaline phosphatase, marker hair inductivity, decreased in DPC spheres treated with DHT, and it was restored by the addition of BMP2.