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Skin And Organoid

Jinmei Diao, Juan Liu, Shuyong Wang, Mingyang Chang, Xuan Wang, Baolin Guo, Qunfang Yu, Fang Yan, Yuxin Su, Yunfang Wang
Sweat glands perform a vital thermoregulatory function in mammals. Like other skin components, they originate from epidermal progenitors. However, they have low regenerative potential in response to injury. We have established a sweat gland culture and expansion method using 3D organoids cultures. The epithelial cells derived from sweat glands in dermis of adult mouse paw pads were embedded into Matrigel and formed sweat gland organoids (SGOs). These organoids maintained remarkable stem cell features and demonstrated differentiation capacity to give rise to either sweat gland cells (SGCs) or epidermal cells...
March 11, 2019: Cell Death & Disease
Maribanyana Lebeko, Nonhlanhla P Khumalo, Ardeshir Bayat
Keloid scars are described as benign fibro-proliferative dermal outgrowths that commonly occur in pigmented skin post cutaneous injury, and continue to grow beyond the boundary of the original wound margin. There is a lack of thorough understanding of keloid pathogenesis and thus keloid therapeutic options remain ill-defined. In view of the poor response to current therapy and high recurrence rates, there is an unmet need in improving our knowledge and therefore in identifying targeted and effective treatment strategies in management of keloids...
February 13, 2019: Wound Repair and Regeneration
Erin L Weber, Thomas E Woolley, Chao-Yuan Yeh, Kuang-Ling Ou, Philip K Maini, Cheng-Ming Chuong
Human skin progenitor cells will form new hair follicles, although at a low efficiency, when injected into nude mouse skin. To better study and improve upon this regenerative process, we developed an in vitro system to analyze the morphogenetic cell behavior in detail and modulate physical-chemical parameters to more effectively generate hair primordia. In this three-dimensional culture, dissociated human neonatal foreskin keratinocytes self-assembled into a planar epidermal layer while fetal scalp dermal cells coalesced into stripes, then large clusters, and finally small clusters resembling dermal condensations...
January 25, 2019: Experimental Dermatology
Basak Icli, Winona Wu, Denizhan Ozdemir, Hao Li, Stefan Haemmig, Xin Liu, Giorgio Giatsidis, Henry S Cheng, Seyma Nazli Avci, Merve Kurt, Nathan Lee, Raphael Boesche Guimaraes, Andre Manica, Julio F Marchini, Stein Erik Rynning, Ivar Risnes, Ivana Hollan, Kevin Croce, Dennis P Orgill, Mark W Feinberg
Angiogenesis is a critical process in repair of tissue injury that is regulated by a delicate balance between pro- and antiangiogenic factors. In disease states associated with impaired angiogenesis, we identified that miR-135a-3p is rapidly induced and serves as an antiangiogenic microRNA (miRNA) by targeting endothelial cell (EC) p38 signaling in vitro and in vivo. MiR-135a-3p overexpression significantly inhibited EC proliferation, migration, and network tube formation in matrigel, whereas miR-135-3p neutralization had the opposite effects...
January 22, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Romina Fiorotto, Mariangela Amenduni, Valeria Mariotti, Luca Fabris, Carlo Spirli, Mario Strazzabosco
Liver diseases negatively impact the quality of life and survival of patients, and often require liver transplantation in cases that progress to organ failure. Understanding the cellular and molecular mechanisms of liver development and pathogenesis has been a challenging task, in part for the lack of adequate cellular models directly relevant to the human diseases. Recent technological advances in the stem cell field have shown the potentiality of induced pluripotent stem cells (iPSC) and liver organoids as the next generation tool to model in vitro liver diseases...
September 5, 2018: Biochimica et Biophysica Acta. Molecular Basis of Disease
Yena Kim, Narae Park, Yeri Alice Rim, Yoojun Nam, Hyerin Jung, Kijun Lee, Ji Hyeon Ju
BACKGROUND: Skin is an organ that plays an important role as a physical barrier and has many other complex functions. Skin mimetics may be useful for studying the pathophysiology of diseases in vitro and for repairing lesions in vivo. Cord blood mononuclear cells (CBMCs) have emerged as a potential cell source for regenerative medicine. Human induced pluripotent stem cells (iPSCs) derived from CBMCs have great potential for allogenic regenerative medicine. Further study is needed on skin differentiation using CBMC-iPSCs...
August 13, 2018: Stem Cell Research & Therapy
Dominique J Wiener, Onur Basak, Priyanca Asra, Kim E Boonekamp, Kai Kretzschmar, Angelos Papaspyropoulos, Hans Clevers
BACKGROUND: Perturbations of epidermal and follicular homeostasis have been attributed to a variety of skin diseases affecting dogs. The availability of an in vitro system to investigate these diseases is important to understand underlying pathomechanisms. OBJECTIVES: To establish an accurate and reliable in vitro 3D system of canine keratinocyte organoids to lay the basis for studying functional defects in interfollicular epidermis (IFE) and hair follicle (HF) morphogenesis, reconstitution and differentiation that lead to alopecic and epidermal diseases...
October 2018: Veterinary Dermatology
Zhuzhen Zhang, Zhenzhen Zi, Eunice E Lee, Jiawei Zhao, Diana C Contreras, Andrew P South, E Dale Abel, Benjamin F Chong, Travis Vandergriff, Gregory A Hosler, Philipp E Scherer, Marcel Mettlen, Jeffrey C Rathmell, Ralph J DeBerardinis, Richard C Wang
Proliferating cells, compared with quiescent cells, are more dependent on glucose for their growth. Although glucose transport in keratinocytes is mediated largely by the Glut1 facilitative transporter, we found that keratinocyte-specific ablation of Glut1 did not compromise mouse skin development and homeostasis. Ex vivo metabolic profiling revealed altered sphingolipid, hexose, amino acid, and nucleotide metabolism in Glut1-deficient keratinocytes, thus suggesting metabolic adaptation. However, cultured Glut1-deficient keratinocytes displayed metabolic and oxidative stress and impaired proliferation...
May 2018: Nature Medicine
Jiyoon Lee, Robert Bӧscke, Pei-Ciao Tang, Byron H Hartman, Stefan Heller, Karl R Koehler
The mammalian hair follicle arises during embryonic development from coordinated interactions between the epidermis and dermis. It is currently unclear how to recapitulate hair follicle induction in pluripotent stem cell cultures for use in basic research studies or in vitro drug testing. To date, generation of hair follicles in vitro has only been possible using primary cells isolated from embryonic skin, cultured alone or in a co-culture with stem cell-derived cells, combined with in vivo transplantation...
January 2, 2018: Cell Reports
Robert E Hynds, Paola Bonfanti, Sam M Janes
More than 40 years ago, Howard Green's laboratory developed a method for long-term expansion of primary human epidermal keratinocytes by co-culture with 3T3 mouse embryonic fibroblasts. This was a breakthrough for in vitro cultivation of cells from human skin and later for other epithelia: it led to the first stem cell therapy using cultured cells and has vastly increased our understanding of epithelial stem cell biology. In recent years, new methods to expand epithelial cells as three-dimensional organoids have provided novel means to investigate the functions of these cells in health and disease...
February 2018: EMBO Molecular Medicine
Ekaterina Kalabusheva, Vasily Terskikh, Ekaterina Vorotelyak
Hair follicle (HF) reconstruction in vitro is a promising field in alopecia treatment and human HF development research. Here, we combined postnatal human dermal papilla (DP) cells and skin epidermal keratinocytes (KCs) in a hanging drop culture to develop an artificial HF germ. The method is based on DP cell hair-inducing properties and KC self-organization. We evaluated two protocols of aggregate assembling. Mixed HF germ-like structures demonstrated the initiation of epithelial-mesenchymal interaction, including WNT pathway activation and expression of follicular markers...
2017: Stem Cells International
David E Watson, Rosemarie Hunziker, John P Wikswo
Microphysiological systems (MPS), which include engineered organoids (EOs), single organ/tissue chips (TCs), and multiple organs interconnected to create miniature in vitro models of human physiological systems, are rapidly becoming effective tools for drug development and the mechanistic understanding of tissue physiology and pathophysiology. The second MPS thematic issue of Experimental Biology and Medicine comprises 15 articles by scientists and engineers from the National Institutes of Health, the IQ Consortium, the Food and Drug Administration, and Environmental Protection Agency, an MPS company, and academia...
October 2017: Experimental Biology and Medicine
Mingxing Lei, Linus J Schumacher, Yung-Chih Lai, Wen-Tau Juan, Chao-Yuan Yeh, Ping Wu, Ting-Xin Jiang, Ruth E Baker, Randall Bruce Widelitz, Li Yang, Cheng-Ming Chuong
Organoids made from dissociated progenitor cells undergo tissue-like organization. This in vitro self-organization process is not identical to embryonic organ formation, but it achieves a similar phenotype in vivo. This implies genetic codes do not specify morphology directly; instead, complex tissue architectures may be achieved through several intermediate layers of cross talk between genetic information and biophysical processes. Here we use newborn and adult skin organoids for analyses. Dissociated cells from newborn mouse skin form hair primordia-bearing organoids that grow hairs robustly in vivo after transplantation to nude mice...
August 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
Wei Xie, Yunfan Yang, Siqi Gao, Ting Song, Yuhan Wu, Dengwen Li, Min Liu, Jun Zhou
Epithelial morphogenesis and homeostasis are essential for animal development and tissue regeneration, and epithelial disorganization is associated with developmental disorders and tumorigenesis. However, the molecular mechanisms that contribute to the morphogenesis and homeostasis of the epithelium remain elusive. Herein, we report a novel role for the cylindromatosis (CYLD) tumor suppressor in these events. Our results show that CYLD depletion disrupts epithelial organization in both Drosophila egg chambers and mouse skin and intestinal epithelia...
July 20, 2017: Journal of Genetics and Genomics
Tiziana A L Brevini, Elena F M Manzoni, Sergio Ledda, Fulvio Gandolfi
Cell remarkable ability to self-organize and rearrange in functional organoids has been greatly boosted by the recent advances in 3-D culture technologies and materials. This approach can be presently applied to model human organ development and function "in a dish" and to predict drug response in a patient specific fashion.Here we describe a protocol that allows for the derivation of functional pancreatic mini-organoids from skin biopsies. Cells are suspended in a drop of medium and encapsulated with hydrophobic polytetrafluoroethylene (PTFE) powder particles, to form microbioreactors defined as "Liquid Marbles," that stimulate cell coalescence and 3-D aggregation...
July 13, 2017: Methods in Molecular Biology
Kotaro Nagase, Hiromi Kimura, Naomi Yonekura, Shinichi Koba, Takuya Inoue, Yutaka Narisawa
Large-cell neuroendocrine carcinoma (LCNEC) is an uncommon and aggressive neuroendocrine tumor, found mainly in the lung. Although LCNEC has been reported in various organs, LCNEC of the skin is extremely rare, poorly recognized and probably underestimated. Here we report a case of LCNEC of the skin, focusing on the histopathological and ultrastructural findings in detail. The patient was an 85-year-old Japanese woman presented with a mass on her right upper eyelid. Biopsy specimen showed an infiltrative mass with extension into the subcutis...
November 2016: Journal of Cutaneous Pathology
Luke A Wiley, Erin R Burnight, Adam P DeLuca, Kristin R Anfinson, Cathryn M Cranston, Emily E Kaalberg, Jessica A Penticoff, Louisa M Affatigato, Robert F Mullins, Edwin M Stone, Budd A Tucker
Immunologically-matched, induced pluripotent stem cell (iPSC)-derived photoreceptor precursor cells have the potential to restore vision to patients with retinal degenerative diseases like retinitis pigmentosa. The purpose of this study was to develop clinically-compatible methods for manufacturing photoreceptor precursor cells from adult skin in a non-profit cGMP environment. Biopsies were obtained from 35 adult patients with inherited retinal degeneration and fibroblast lines were established under ISO class 5 cGMP conditions...
July 29, 2016: Scientific Reports
Michele Solis
Since the 1980s, stem cells' shape-shifting abilities have wowed scientists. With proper handling, a few growth factors, and some time, stem cells can be cooked up into specific cell types, including neurons, muscle, and skin.
July 2016: IEEE Pulse
Fernanda R Cugola, Isabella R Fernandes, Fabiele B Russo, Beatriz C Freitas, João L M Dias, Katia P Guimarães, Cecília Benazzato, Nathalia Almeida, Graciela C Pignatari, Sarah Romero, Carolina M Polonio, Isabela Cunha, Carla L Freitas, Wesley N Brandão, Cristiano Rossato, David G Andrade, Daniele de P Faria, Alexandre T Garcez, Carlos A Buchpigel, Carla T Braconi, Erica Mendes, Amadou A Sall, Paolo M de A Zanotto, Jean Pierre S Peron, Alysson R Muotri, Patricia C B Beltrão-Braga
Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (family Flaviviridae) and was first described in 1947 in Uganda following blood analyses of sentinel Rhesus monkeys. Until the twentieth century, the African and Asian lineages of the virus did not cause meaningful infections in humans. However, in 2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy epidemic on the Yap Island in Micronesia. Patients experienced fever, skin rash, arthralgia and conjunctivitis. From 2013 to 2015, the Asian lineage of the virus caused further massive outbreaks in New Caledonia and French Polynesia...
June 9, 2016: Nature
Vera Chesnokova, Svetlana Zonis, Cuiqi Zhou, Maria Victoria Recouvreux, Anat Ben-Shlomo, Takako Araki, Robert Barrett, Michael Workman, Kolja Wawrowsky, Vladimir A Ljubimov, Magdalena Uhart, Shlomo Melmed
Growth hormone (GH) excess in acromegaly is associated with increased precancerous colon polyps and soft tissue adenomas, whereas short-stature humans harboring an inactivating GH receptor mutation do not develop cancer. We show that locally expressed colon GH is abundant in conditions predisposing to colon cancer and in colon adenocarcinoma-associated stromal fibroblasts. Administration of a GH receptor (GHR) blocker in acromegaly patients induced colon p53 and adenomatous polyposis coli (APC), reversing progrowth GH signals...
June 7, 2016: Proceedings of the National Academy of Sciences of the United States of America
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