scholarly journals Dermal Pericytes Exhibit Declined Ability to Promote Human Skin Regeneration with Ageing in 3D Organotypic Culture Models

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3051
Author(s):  
Lizhe Zhuang ◽  
Rahul M. Visalakshan ◽  
Pritinder Kaur
Keyword(s):  
Human Skin ◽  
Basal Layer ◽  
Nutrient Sensing ◽  
Skin Regeneration ◽  
Telomere Shortening ◽  
Culture Model ◽  
Culture Models ◽  
And Function ◽  
Dermal Cells ◽  
Epidermal Regeneration

The well documented decline in the regenerative ability of ageing human skin has been attributed to many factors including genomic instability, telomere shortening, poor nutrient sensing, cellular senescence, and stem cell exhaustion. However, a role for the dermal cellular and molecular microenvironment in skin ageing is just emerging. We previously showed that dermal pericytes co-operate with fibroblasts to improve human skin regeneration in an organotypic skin culture model, and even do so in the absence of fibroblasts. Here, we report that the number of dermal cells, particularly pericytes, declines significantly in human skin of donors aged > 50 years. Notably, aged pericytes promoted epidermal regeneration of neonatal keratinocytes in organotypic cultures and the resulting epithelium exhibited a Ki67+/ΔNp63+ basal layer and terminal differentiation. However, the epithelium lacked several features of homeostasis displaying lower levels of ΔNp63 expression, decreased LAMA5 deposition at the dermo-epidermal junction, and the absence of basement membrane and hemi-desmosome assembly. We conclude that a decline in pericyte incidence and function contribute to an impaired epidermal microenvironment and poor skin regeneration with ageing in the human skin.

Localization of Merkel cells at hairless and hairy human skin sites using keratin 18

1995 ◽  
Vol 73 (9-10) ◽  
pp. 635-639 ◽  
Author(s):  
Julie Fradette ◽  
Marie-Josée Godbout ◽  
Martine Michel ◽  
Lucie Germain
Keyword(s):  
Human Skin ◽  
Basal Layer ◽  
Sensory Nerve ◽  
Neurosecretory Cells ◽  
Nerve Fibers ◽  
Hair Follicles ◽  
Merkel Cells ◽  
Merkel Cell ◽  
Skin Receptor ◽  
And Function

Merkel cells are neurosecretory cells of the skin with epithelial features such as desmosomes and expression of keratins 8, 18, 19, and 20. Merkel cells are scarcely distributed in adult human skin. Although they are present in hair follicles, their density is higher at hairless anatomic sites such as palms and soles. These cells are often innervated by sensory nerve fibers and are thought to be specialized mechanosensory skin receptor cells. However, their precise origin and function are not clearly established. The aim of this study was to localize Merkel cells in human hairless and hairy skin by immunohistochemistry with antibodies Ks18.174 and Ks19.1 directed against keratins 18 and 19, respectively. In glabrous skin of palm and sole, Merkel cells have been localized at the bottom of the rete ridges, in the epidermal basal layer. To study Merkel cell distribution at hairy anatomic sites, we have chosen breast skin, a tissue containing small hair follicles typical of those covering most of the body's surface. Merkel cells were present in the interfollicular epidermis. In hair follicles, they have been identified in the isthmus region.Key words: skin, human, Merkel cell, keratin, hair follicle.

scholarly journals Murine ex vivo cultured alveolar macrophages provide a novel tool to study tissue-resident macrophage behavior and function

2021 ◽  
Author(s):  
A.-D. Gorki ◽  
D. Symmank ◽  
S. Zahalka ◽  
K. Lakovits ◽  
A. Hladik ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Ex Vivo ◽  
List Type ◽  
Gm Csf ◽  
Culture Model ◽  
Versatile Tool ◽  
Culture Models ◽  
Novel Method ◽  
And Function

SUMMARYTissue-resident macrophages are of vital importance as they preserve tissue homeostasis in all mammalian organs. Nevertheless, appropriate cell culture models are still limited. Here, we propose a novel culture model to study and expand murine primary alveolar macrophages (AMs), the tissue-resident macrophages of the lung, in vitro over several months. By providing a combination of GM-CSF, TGFβ and the PPARγ activator rosiglitazone, we maintain and expand mouse ex vivo cultured AMs, short mexAMs, over several months. MexAMs maintain typical morphologic features and stably express primary AM surface markers throughout in vitro culture. They respond to microbial ligands and exhibit an AM-like transcriptional profile, including the expression of AM specific transcription factors. Furthermore, when transferred into AM deficient mice, mexAMs efficiently engraft in the lung and fulfill key macrophage functions leading to a significantly reduced surfactant load in those mice. Altogether, mexAMs provide a novel, simple and versatile tool to study AM behavior in homeostasis and disease settings.KEYPOINTSA novel method to culture and expand primary alveolar macrophages over several months ex vivoMurine ex vivo cultured alveolar macrophages (mexAMs) restore lung function in a murine pulmonary alveolar proteinosis model

Desmosomal distribution in the epidermis of a non-contracting human skin equivalent

1992 ◽  
Vol 50 (1) ◽  
pp. 896-897
Author(s):  
L.X. Oakford ◽  
S.D. Dimitrijevich ◽  
R. Gracy
Keyword(s):  
Human Skin ◽  
Basal Layer ◽  
Skin Equivalent ◽  
Tissue Component ◽  
Intact Skin ◽  
Similar Sequence ◽  
Sequence Of Events ◽  
Suprabasal Keratinocytes ◽  
Human Skin Equivalent

In intact skin the epidermal layer is a dynamic tissue component which is maintained by a basal layer of mitotically active cells. The protective upper epidermis, the stratum corneum, is generated by differentiation of the suprabasal keratinocytes which eventually desquamate as anuclear comeocytes. A similar sequence of events is observed in vitro in the non-contracting human skin equivalent (HSE) which was developed in this lab (1). As a part of the definition process for this model of living skin we are examining its ultrastructural features. Since desmosomes are important in maintaining cell-cell interactions in stratified epithelia their distribution in HSE was examined.

scholarly journals Bisphosphonates Reduce Smoking-Induced Osteoporotic-Like Alterations by Regulating RANKL/OPG in an Osteoblast and Osteoclast Co-Culture Model

2020 ◽  
Vol 22 (1) ◽  
pp. 53
Author(s):  
Sheng Zhu ◽  
Victor Häussling ◽  
Romina H. Aspera-Werz ◽  
Tao Chen ◽  
Bianca Braun ◽  
...  
Keyword(s):  
Alternative Therapy ◽  
Cigarette Smoke Extract ◽  
Matrix Remodeling ◽  
Nuclear Factor ◽  
Bone Homeostasis ◽  
Potential Mechanism ◽  
Culture Model ◽  
Receptor Activator ◽  
Culture Models

Co-culture models have become mandatory for obtaining better insights into bone homeostasis, which relies on the balance between osteoblasts and osteoclasts. Cigarette smoking (CS) has been proven to increase the risk of osteoporosis; however, there is currently no proven treatment for osteoporosis in smokers excluding cessation. Bisphosphonates (BPs) are classical anti-osteoclastic drugs that are commonly used in examining the suitability of bone co-culture systems in vitro as well as to verify the response to osteoporotic stimuli. In the present study, we tested the effects of BPs on cigarette smoke extract (CSE)-affected cells in the co-culture of osteoblasts and osteoclasts. Our results showed that BPs were able to reduce CSE-induced osteoporotic alterations in the co-culture of osteoblasts and osteoclasts such as decreased matrix remodeling, enhanced osteoclast activation, and an up-regulated receptor activator of nuclear factor (NF)-kB-ligand (RANKL)/osteoprotegerin (OPG) ratio. In summary, BPs may be an effective alternative therapy for reversing osteoporotic alterations in smokers, and the potential mechanism is through modulation of the RANKL/OPG ratio.

scholarly journals Characterization of a Primate Blood-Brain Barrier Co-Culture Model Prepared from Primary Brain Endothelial Cells, Pericytes and Astrocytes

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1484
Author(s):  
Daisuke Watanabe ◽  
Shinsuke Nakagawa ◽  
Yoichi Morofuji ◽  
Andrea E. Tóth ◽  
Monika Vastag ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Transport Systems ◽  
Brain Endothelial Cells ◽  
Monkey Brain ◽  
Blood Brain ◽  
Culture Model ◽  
Culture Models ◽  
Human Primate

Culture models of the blood-brain barrier (BBB) are important research tools. Their role in the preclinical phase of drug development to estimate the permeability for potential neuropharmaceuticals is especially relevant. Since species differences in BBB transport systems exist, primate models are considered as predictive for drug transport to brain in humans. Based on our previous expertise we have developed and characterized a non-human primate co-culture BBB model using primary cultures of monkey brain endothelial cells, rat brain pericytes, and rat astrocytes. Monkey brain endothelial cells in the presence of both pericytes and astrocytes (EPA model) expressed enhanced barrier properties and increased levels of tight junction proteins occludin, claudin-5, and ZO-1. Co-culture conditions also elevated the expression of key BBB influx and efflux transporters, including glucose transporter-1, MFSD2A, ABCB1, and ABCG2. The correlation between the endothelial permeability coefficients of 10 well known drugs was higher (R2 = 0.8788) when the monkey and rat BBB culture models were compared than when the monkey culture model was compared to mouse in vivo data (R2 = 0.6619), hinting at transporter differences. The applicability of the new non-human primate model in drug discovery has been proven in several studies.

Melanocyte Distribution and Function in Human Skin

2007 ◽  
pp. 101-115 ◽  
Author(s):  
Yuji Yamaguchi ◽  
Vincent J. Hearing
Keyword(s):  
Human Skin ◽  
And Function

scholarly journals Skin Regeneration Effect and Chemical Composition of Essential Oil from Artemisia montana

2014 ◽  
Vol 9 (11) ◽  
pp. 1934578X1400901 ◽  
Author(s):  
Mi-So Yoon ◽  
Kyung-Jong Won ◽  
Do Yoon Kim ◽  
Dae il Hwang ◽  
Seok Won Yoon ◽  
...  
Keyword(s):  
Essential Oil ◽  
Human Skin ◽  
Type Iv Collagen ◽  
Steam Distillation ◽  
Biological Effects ◽  
Skin Regeneration ◽  
Type I ◽  
Dependent Manner ◽  
Positive Effects ◽  
Type Iv

Artemisia montana Pampan (Compositae) (AMP) contains various compounds, including phenolic acids, alkaloids, and essential oil. It has been widely used in oriental medicine due to a variety of biological effects. However, the biological activity of the essential oil from AMP (AMPEO) on skin has not been investigated. In the present study, AMPEO was evaluated for its composition and its effect on cellular events (migration and proliferation) related to skin regeneration using normal human keratinocytes (HaCats). AMPEO, which was extracted by steam distillation, contained 42 components. AMPEO increased proliferation in HaCats in a dose-dependent manner (EC 50, 8.5 ng/mL) and did not affect migration. AMPEO also enhanced the phosphorylation of Akt and ERK 1/2 and induced the synthesis of type IV collagen, but not type I collagen in HaCats. In addition, AMPEO promoted wound closure in the dorsal side skin of rat tail. These results demonstrated that AMPEO extracted by steam distillation induced proliferation and synthesis of type IV collagen in human skin keratinocytes, and may thereby exert positive effects on skin regeneration and wound healing in human skin.

scholarly journals A novel nutrient sensing mechanism underlies substrate-induced regulation of monocarboxylate transporter-1

2012 ◽  
Vol 303 (10) ◽  
pp. G1126-G1133 ◽  
Author(s):  
Alip Borthakur ◽  
Shubha Priyamvada ◽  
Anoop Kumar ◽  
Arivarasu A. Natarajan ◽  
Ravinder K. Gill ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Apical Membrane ◽  
Nutrient Sensing ◽  
Monocarboxylate Transporter ◽  
Rat Colon ◽  
Intracellular Camp ◽  
Short Term ◽  
Monocarboxylate Transporter 1 ◽  
Sensing Mechanism ◽  
And Function

Monocarboxylate transporter isoform-1 (MCT1) plays an important role in the absorption of short-chain fatty acids (SCFAs) in the colon. Butyrate, a major SCFA, serves as the primary energy source for the colonic mucosa, maintains epithelial integrity, and ameliorates intestinal inflammation. Previous studies have shown substrate (butyrate)-induced upregulation of MCT1 expression and function via transcriptional mechanisms. The present studies provide evidence that short-term MCT1 regulation by substrates could be mediated via a novel nutrient sensing mechanism. Short-term regulation of MCT1 by butyrate was examined in vitro in human intestinal C2BBe1 and rat intestinal IEC-6 cells and ex vivo in rat intestinal mucosa. Effects of pectin feeding on MCT1, in vivo, were determined in rat model. Butyrate treatment (30–120 min) of C2BBe1 cells increased MCT1 function {p-(chloromercuri) benzene sulfonate (PCMBS)-sensitive [14C]butyrate uptake} in a pertussis toxin-sensitive manner. The effects were associated with decreased intracellular cAMP levels, increased Vmax of butyrate uptake, and GPR109A-dependent increase in apical membrane MCT1 level. Nicotinic acid, an agonist for the SCFA receptor GPR109A, also increased MCT1 function and decreased intracellular cAMP. Pectin feeding increased apical membrane MCT1 levels and nicotinate-induced transepithelial butyrate flux in rat colon. Our data provide strong evidence for substrate-induced enhancement of MCT1 surface expression and function via a novel nutrient sensing mechanism involving GPR109A as a SCFA sensor.

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