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Dermal fibroblast

Elham Farhadi, Mahdi Mahmoudi, Farzaneh Rahmani, Bahman Yousefi, Abdolfattah Sarafnejad, Hoda Kavosi, Elham Karimizadeh, Ahmadreza Jamshidi, Farhad Gharibdoost
OBJECTIVES: Impaired wound healing and skin dehydration are the mainstay of systemic sclerosis (SSc) cutaneous manifestations. Aquaporin-3 (AQP3) has a pivotal role in skin hydration and wound healing. Epidermal growth factor receptor (EGFR) activation is impaired in SSc fibroblasts. It is unclear whether AQP3 downregulation or epidermal growth factor (EGF) signaling are the primary points of dysregulation in SSc patients. METHODS: Skin punch biopsies were obtained from 10 SSc patients and 10 healthy subjects...
December 7, 2018: Journal of Cellular Physiology
Patrick S McGrath, Nicole Diette, Igor Kogut, Ganna Bilousova
Induced pluripotent stem cells (iPSCs) have proven to be a valuable tool to study human development and disease. Further advancing iPSCs as a regenerative therapeutic requires a safe, robust, and expedient reprogramming protocol. Here, we present a clinically relevant, step-by-step protocol for the extremely high-efficiency reprogramming of human dermal fibroblasts into iPSCs using a non-integrating approach. The core of the protocol consists of expressing pluripotency factors (SOX2, KLF4, cMYC, LIN28A, NANOG, OCT4-MyoD fusion) from in vitro transcribed messenger RNAs synthesized with modified nucleotides (modified mRNAs)...
November 26, 2018: Journal of Visualized Experiments: JoVE
Qingmei Liu, Jiaying Lu, Jinran Lin, Yulong Tang, Weilin Pu, Xiangguang Shi, Shuai Jiang, Jing Liu, Yanyun Ma, Yuan Li, Jinhua Xu, Li Jin, Jiucun Wang, Wenyu Wu
Systemic sclerosis (SSc) is a connective tissue disease characterized mainly by fibrosis of skin and internal organs. Our previous study has shown that salvianolic acid B (SAB), a bioactive component extracted from Salvia miltiorrhiza (SM), was one of the essential ingredients in the traditional Chinese medicine Yiqihuoxue formula, which has been used to treat SSc-related dermal and pulmonary fibrosis. The aim of the present study was to evaluate the effect of SAB on skin fibrosis and explore its underlying anti-fibrotic mechanism...
December 7, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Steffen Nielsen, Niels Bassler, Leszek Grzanka, Louise Laursen, Jan Swakon, Pawel Olko, Christian Nicolaj Andreassen, Jan Alsner, Brita Sørensen
PURPOSE: To identify differential cellular responses following proton and photon irradiation by comparing transcriptomes of primary fibroblasts irradiated with either radiation type. METHODS AND MATERIALS: A panel of primary dermal fibroblast cultures were irradiated with low and higher LET proton beams. Cobalt-60 photon irradiation was used as reference. Dose was delivered in 3 fractions x 3.5 Gy(RBE) using a RBE of 1.1 for proton doses. Cells were harvested 2 hours after the final fraction was delivered and RNA was purified...
December 6, 2018: International Journal of Radiation Oncology, Biology, Physics
Joseph J Chin, Babak Behnam, Mariska Davids, Prashant Sharma, Wadih M Zein, Camille Wang, Xenia Chepa-Lotrea, William Brian Gallantine, Camilo Toro, David R Adams, Cynthia J Tifft, William A Gahl, May Christine V Malicdan
CLN6 is a transmembrane protein located in the endoplasmic reticulum that is involved in lysosomal acidification. Mutations in CLN6 cause late-infantile neuronal ceroid lipofuscinosis (LINCL), and teenage and adult onset NCL without visual impairment. Here we describe two pediatric patients with LINCL from unrelated families who were evaluated at the National Institutes of Health. Both children exhibited typical phenotypes associated with LINCL except that they lacked the expected visual impairment. Whole exome sequencing identified novel biallelic mutations in CLN6, i...
December 3, 2018: Molecular Genetics and Metabolism
Francesca Cianfarani, Emanuela De Domenico, Alexander Nyström, Simona Mastroeni, Damiano Abeni, Enke Baldini, Salvatore Ulisse, Paolo Uva, Leena Bruckner-Tuderman, Giovanna Zambruno, Daniele Castiglia, Teresa Odorisio
Loss-of-function mutations in the gene encoding type VII collagen underlie recessive dystrophic epidermolysis bullosa (RDEB), a disease characterized by skin and mucosal blistering, impaired wound healing, and diffuse dermal inflammation and fibrosis. Transforming growth factor-β signaling plays a crucial role in determining RDEB fibrotic microenvironment that leads to the development of disabling secondary disease manifestations, including hand and foot deformities. Experimental findings indicate that expression levels of decorin, a small leucine-rich proteoglycan and an endogenous TGF-β inhibitor, can modulate RDEB disease phenotype by contrasting dermal fibroblast fibrotic behavior...
December 5, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Ellen Witte-Händel, Kerstin Wolk, Athanasia Tsaousi, Marie Luise Irmer, Rotraut Mößner, Orr Shomroni, Thomas Lingner, Katrin Witte, Desiree Kunkel, Gabriela Salinas, Stefan Jodl, Nicole Schmidt, Wolfram Sterry, Hans-Dieter Volk, Evangelos J Giamarellos-Bourboulis, Anna Pokrywka, Wolf-Dietrich Döcke, Sylke Schneider-Burrus, Robert Sabat
Hidradenitis suppurativa (HS; also designated as acne inversa) is a chronic inflammatory disease characterized by painful purulent skin lesions and progressive destruction of skin architecture. Despite the high burden for the patients, pathogenetic pathways underlying HS alterations remain obscure. Investigating the lesional HS cytokine pattern, IL-1β turned out as a highly prominent cytokine, being overexpressed even compared to psoriatic lesions. Analyses of IL-1β-induced transcriptome in various cell types disclosed an overlap of upregulated molecules causing immune cell infiltration and extracellular matrix degradation, as well as of specific cytokines including IL-6, IL-32, and IL-36...
December 5, 2018: Journal of Investigative Dermatology
Peilong Lai, Xiaomei Chen, Liyan Guo, Yulian Wang, Xialin Liu, Yan Liu, Tian Zhou, Tian Huang, Suxia Geng, Chengwei Luo, Xin Huang, Suijing Wu, Wei Ling, Xin Du, Chang He, Jianyu Weng
BACKGROUND: Mesenchymal stromal cells (MSCs) are a promising therapy for preventing chronic Graft-Versus-Host Disease (cGVHD) due to their potent immunomodulatory properties. However, the safety concerns regarding the use of MSCs remain unsolved, and conflicting effects are observed due to the heterogeneity of MSCs. Recently, exosomes were shown to mediate the paracrine effects of MSCs, making it a potential candidate for cell-free therapies. The aim of this study is to investigate the efficacy and safety of MSCs-derived exosomes (MSCs-exo) in an established cGVHD mouse model...
December 7, 2018: Journal of Hematology & Oncology
Se-Ho Park, Seung-Su Lee, Myun-Ho Bang, Sung Kwan Jo, Kwang-Hwan Jhee, Seun-Ah Yang
This study was undertaken to determine the effects of enzyme-treated Zizania latifolia (ETZL) and of its major compound tricin on skin photo-aging and to investigate the mechanisms involved. It was found ETZL and tricin suppressed matrix metalloproteinase (MMP) production and increased type I-procollagen production in UVB-irradiated human dermal fibroblasts (HDFs). Furthermore, ETZL and tricin significantly up-regulated the expressions of the antioxidant enzymes HO-1 and SOD1, reduced UVB-induced reactive oxygen species (ROS) generation and mitogen-activated protein kinase (MAPK) induction by ROS and thereby attenuated activator protein-1 (AP-1) expression...
December 9, 2018: Bioscience, Biotechnology, and Biochemistry
William S Boyle, Kirk Twaroski, Emily C Woska, Jakub Tolar, Theresa M Reineke
Fast, efficient, and inexpensive methods for delivering functional nucleic acids to primary human cell types are needed to advance regenerative medicine and cell therapies. Plasmid-based gene editing (such as with CRISPR-Cas9) can require the delivery of plasmids that are large (∼9.5-13 kbp) in comparison to common reporter plasmids (∼5-8 kbp). To develop more efficient plasmid delivery vehicles, we investigated the effect of plasmid size on the transfection of primary human dermal fibroblasts (HDFs) and induced pluripotent stem cells (iPSCs) using a heparin-treated trehalose-containing polycation (Tr4-heparin)...
December 10, 2018: Bioconjugate Chemistry
Malgorzata Czyz
Hepatocyte growth factor (HGF)/ mesenchymal-epithelial transition factor (c-MET) signaling is involved in complex cellular programs that are important for embryonic development and tissue regeneration, but its activity is also utilized by cancer cells during tumor progression. HGF and c-MET usually mediate heterotypic cell⁻cell interactions, such as epithelial⁻mesenchymal, including tumor⁻stroma interactions. In the skin, dermal fibroblasts are the main source of HGF. The presence of c-MET on keratinocytes is crucial for wound healing in the skin...
December 3, 2018: International Journal of Molecular Sciences
Abha Sahni, Hema P Narra, Jignesh Patel, Sanjeev K Sahni
Microvascular endothelial cells (ECs) represent the primary target cells during human rickettsioses and respond to infection via the activation of immediate⁻early signaling cascades and the resultant induction of gene expression. As small noncoding RNAs dispersed throughout the genome, microRNAs (miRNAs) regulate gene expression post-transcriptionally to govern a wide range of biological processes. Based on our recent findings demonstrating the involvement of fibroblast growth factor receptor 1 (FGFR1) in facilitating rickettsial invasion into host cells and published reports suggesting miR-424 and miR-503 as regulators of FGF2/FGFR1, we measured the expression of miR-424 and miR-503 during R...
December 1, 2018: Cells
Mariam Gaid, Jendrik Füller, Christel Müller-Goymann
The hyperforin content of Hypericum perforatum herb was repeatedly reported to be responsible for a multitude of pharmacological activities. Our recent report about the hyperforin accumulation in in vitro root cultures of H. perforatum provides an alternative perspective to achieve constant product quality and to serve the rapidly growing market. In this study, the antiproliferative effect of a petroleum ether extract from the in vitro root cultures was investigated. When normalized to 1 µM hyperforin content, the extract reduced the viability of human keratinocytes (HaCaT) and human dermal fibroblast monolayers to 33 and 36%, respectively, after 72 h of incubation...
December 4, 2018: Planta Medica
Sahar Biglari, Thi Y L Le, Richard P Tan, Steven G Wise, Alessandro Zambon, Gaia Codolo, Marina De Bernard, Majid Warkiani, Aaron Schindeler, Sina Naficy, Peter Valtchev, Ali Khademhosseini, Fariba Dehghani
Considerable progress has been made in the field of microfluidics to develop complex systems for modeling human skin and dermal wound healing processes. While microfluidic models have attempted to integrate multiple cell types and/or 3D culture systems, to date they have lacked some elements needed to fully represent dermal wound healing. This paper describes a cost-effective, multicellular microfluidic system that mimics the paracrine component of early inflammation close to normal wound healing. Collagen and Matrigel are tested as materials for coating and adhesion of dermal fibroblasts and human umbilical vein endothelial cells (HUVECs)...
December 4, 2018: Advanced Healthcare Materials
Clive J Curley, Eimear B Dolan, Matthias Otten, Svenja Hinderer, Garry P Duffy, Bruce P Murphy
As treatments for myocardial infarction (MI) continue to improve, the population of people suffering from heart failure (HF) is rising significantly. Novel treatment strategies aimed at achieving long-term functional stabilisation and improvement in heart function post MI include the delivery of biomaterial hydrogels and myocardial matrix-based therapies to the left ventricle wall. Individually alginate hydrogels and myocardial matrix-based therapies are at the most advanced stages of commercial/clinical development for this potential treatment option...
December 3, 2018: Drug Delivery and Translational Research
Katharina Eberhardt, Christian Matthäus, Shiva Marthandan, Stephan Diekmann, Jürgen Popp
Dermal fibroblast cells can adopt different cell states such as proliferation, quiescence, apoptosis or senescence, in order to ensure tissue homeostasis. Proliferating (dividing) cells pass through the phases of the cell cycle, while quiescent and senescent cells exist in a non-proliferating cell cycle-arrested state. However, the reversible quiescence state is in contrast to the irreversible senescence state. Long-term quiescent cells transit into senescence indicating that cells age also when not passing through the cell cycle...
2018: PloS One
Ivo Laidmäe, Kaspars Ērglis, Andrejs Cēbers, Paul A Janmey, Raivo Uibo
3D fibrous scaffolds have received much recent attention in regenerative medicine. Use of fibrous scaffolds has shown promising results in tissue engineering and wound healing. Here we report the development and properties of a novel fibrous scaffold that is useful for promoting wound healing. A scaffold made of salmon fibrinogen and chitosan is produced by electrospinning, resulting in a biocompatible material mimicking the structure of the native extracellular matrix (ECM) with suitable biochemical and mechanical properties...
November 30, 2018: Journal of Materials Science. Materials in Medicine
Jenna N Harvestine, Hakan Orbay, Jonathan Y Chen, David E Sahar, J Kent Leach
Lipoaspirates contain a readily accessible heterogeneous cell source for use in bone regeneration collectively referred to as the stromal vascular fraction (SVF). However, the osteogenic potential of SVF is inferior to other progenitor cell populations, thereby requiring alternative strategies to potentiate its effective use in cell-based therapies of bone repair. Cell-secreted extracellular matrix (ECM) is a promising substrate to guide cell phenotype or for use in biomaterial design, yet the instructional capacity of ECMs produced by various cell types is unknown...
June 28, 2018: Journal of Materials Chemistry. B, Materials for Biology and Medicine
Xi Duan, Tao Wu, Ting Liu, Hao Yang, Xiaojie Ding, Yan Chen, Yunzhu Mu
Exposure of ultraviolet (UV) radiation is the major factor from environment to cause erethema, inflammation, photoaging and skin carcinogenesis. Vicenin-2, a bioflavonoid which are isolated from several medicinal plants. The present study was demonstrated the role of vicenin-2 on UVB linked oxidative stress and photoaging signaling in human dermal fibroblasts (HDF). In this study, UVB-irradiation (100 mJ/cm2 ) significantly elevated the intracellular ROS levels, lipid peroxidation, DNA damage, depletion of antioxidants resulted in apoptotic HDF cells...
November 24, 2018: Journal of Photochemistry and Photobiology. B, Biology
Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Marwa Hussein, Warda Hamitou, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade
Melanoma cell sensitivity to targeted therapy molecules is dependent on the tumor microenvironment (cell-cell and cell-extracellular matrix interactions). Three dimensional (3D) in vitro cell culture systems better reflect the native structural architecture of tissues and are attractive to investigate cellular interactions. We have developed and compared several metastatic melanoma models: melanoma cells (SK-MEL-28 and SK-MEL-3, BRAF V600E mutant and SK-MEL-2 BRAF wt) cultured as a monolayer (2D) and co-cultured on 3D dermal equivalents with fibroblasts to better unravel factors modulating cell sensitivity to a BRAF inhibitor (BRAFi, vemurafenib)...
December 1, 2018: Tissue Engineering. Part A
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