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Article ; Online: Alveolar epithelial progenitor cells require Nkx2-1 to maintain progenitor-specific epigenomic state during lung homeostasis and regeneration.

Toth, Andrea / Kannan, Paranthaman / Snowball, John / Kofron, Matthew / Wayman, Joseph A / Bridges, James P / Miraldi, Emily R / Swarr, Daniel / Zacharias, William J

Nature communications

2023 Volume 14, Issue 1, Page(s) 8452

Abstract: Lung epithelial regeneration after acute injury requires coordination cellular coordination to pattern the morphologically complex alveolar gas exchange surface. During adult lung regeneration, Wnt-responsive alveolar epithelial progenitor (AEP) cells, a ...

Abstract	Lung epithelial regeneration after acute injury requires coordination cellular coordination to pattern the morphologically complex alveolar gas exchange surface. During adult lung regeneration, Wnt-responsive alveolar epithelial progenitor (AEP) cells, a subset of alveolar type 2 (AT2) cells, proliferate and transition to alveolar type 1 (AT1) cells. Here, we report a refined primary murine alveolar organoid, which recapitulates critical aspects of in vivo regeneration. Paired scRNAseq and scATACseq followed by transcriptional regulatory network (TRN) analysis identified two AT1 transition states driven by distinct regulatory networks controlled in part by differential activity of Nkx2-1. Genetic ablation of Nkx2-1 in AEP-derived organoids was sufficient to cause transition to a proliferative stressed Krt8
MeSH term(s)	Animals ; Mice ; Cell Differentiation ; Epigenomics ; Epithelial Cells ; Homeostasis ; Lung ; Stem Cells
Chemical Substances	Nkx2-1 protein, mouse
Language	English
Publishing date	2023-12-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-44184-0
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Article ; Online: Rap1b-loss increases neutrophil lactate dehydrogenase activity to enhance neutrophil migration and acute inflammation

Chowdhury, Chanchal Sur / Wareham, Elizabeth / Xu, Juying / Kumar, Sachin / Kofron, Matthew / Lakshmikanthan, Sribalaji / Chrzanowska, Magdalena / Filippi, Marie-Dominique

Frontiers in immunology

2022 Volume 13, Page(s) 1061544

Abstract: Introduction: Neutrophils are critical for host immune defense; yet, aberrant neutrophil tissue infiltration triggers tissue damage. Neutrophils are heterogeneous functionally, and adopt 'normal' or 'pathogenic' effector function responses. ... ...

Abstract	Introduction: Neutrophils are critical for host immune defense; yet, aberrant neutrophil tissue infiltration triggers tissue damage. Neutrophils are heterogeneous functionally, and adopt 'normal' or 'pathogenic' effector function responses. Understanding neutrophil heterogeneity could provide specificity in targeting inflammation. We previously identified a signaling pathway that suppresses neutrophilmediated inflammation via integrin-mediated Rap1b signaling pathway. Methods: Here, we used Rap1-deficient neutrophils and proteomics to identify pathways that specifically control pathogenic neutrophil effector function. Results: We show neutrophil acidity is normally prevented by Rap1b during normal immune response with loss of Rap1b resulting in increased neutrophil acidity via enhanced Ldha activity and abnormal neutrophil behavior. Acidity drives the formation of abnormal invasive-like protrusions in neutrophils, causing a shift to transcellular migration through endothelial cells. Acidity increases neutrophil extracellular matrix degradation activity and increases vascular leakage in vivo. Pathogenic inflammatory condition of ischemia/reperfusion injury is associated with increased neutrophil transcellular migration and vascular leakage. Reducing acidity with lactate dehydrogenase inhibition in vivo limits tissue infiltration of pathogenic neutrophils but less so of normal neutrophils, and reduces vascular leakage. Discussion: Acidic milieu renders neutrophils more dependent on Ldha activity such that their effector functions are more readily inhibited by small molecule inhibitor of Ldha activity, which offers a therapeutic window for antilactate dehydrogenase treatment in specific targeting of pathogenic neutrophils
Language	English
Publishing date	2022-11-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1061544
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Article ; Online: Multiphoton crosslinking for biocompatible 3D printing of type I collagen.

Bell, Alex / Kofron, Matthew / Nistor, Vasile

Biofabrication

2015 Volume 7, Issue 3, Page(s) 35007

Abstract: Multiphoton fabrication is a powerful technique for three-dimensional (3D) printing of structures at the microscale. Many polymers and proteins have been successfully structured and patterned using this method. Type I collagen comprises a large part of ... ...

Abstract	Multiphoton fabrication is a powerful technique for three-dimensional (3D) printing of structures at the microscale. Many polymers and proteins have been successfully structured and patterned using this method. Type I collagen comprises a large part of the extracellular matrix for most tissue types and is a widely used cellular scaffold material for tissue engineering. Current methods for creating collagen tissue scaffolds do not allow control of local geometry on a cellular scale. This means the environment experienced by cells may be made up of the native material but unrelated to native cellular-scale structure. In this study, we present a novel method to allow multiphoton crosslinking of type I collagen with flavin mononucleotide photosensitizer. The method detailed allows full 3D printing of crosslinked structures made from unmodified type I collagen and uses only demonstrated biocompatible materials. Resolution of 1 μm for both standing lines and high-aspect ratio gaps between structures is demonstrated and complex 3D structures are fabricated. This study demonstrates a means for 3D printing with one of the most widely used tissue scaffold materials. High-resolution, 3D control of the fabrication of collagen scaffolds will facilitate higher fidelity recreation of the native extracellular environment for engineered tissues.
MeSH term(s)	Biocompatible Materials/chemistry ; Bioprinting/methods ; Collagen Type I/chemistry ; Cross-Linking Reagents ; Flavin Mononucleotide ; Photosensitizing Agents ; Printing, Three-Dimensional ; Tissue Engineering/methods ; Tissue Scaffolds/chemistry
Chemical Substances	Biocompatible Materials ; Collagen Type I ; Cross-Linking Reagents ; Photosensitizing Agents ; Flavin Mononucleotide (7N464URE7E)
Language	English
Publishing date	2015-09-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2500944-8
ISSN	1758-5090 ; 1758-5082
ISSN (online)	1758-5090
ISSN	1758-5082
DOI	10.1088/1758-5090/7/3/035007
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Article ; Online: Lipopolysaccharide Reverses Hepatic Stellate Cell Activation Through Modulation of cMyb, Small Mothers Against Decapentaplegic, and CCAAT/Enhancer-Binding Protein C/EBP Transcription Factors.

Sharma, Akanksha / Verma, Alok K / Kofron, Matthew / Kudira, Ramesh / Miethke, Alexander / Wu, Tong / Wang, Jiang / Gandhi, Chandrashekhar R

Hepatology (Baltimore, Md.)

2020 Volume 72, Issue 5, Page(s) 1800–1818

Abstract: Background and aims: During liver injury, quiescent hepatic stellate cells (qHSCs) transdifferentiate into proliferative and fibrogenic activated myofibroblastic phenotype (activated hepatic stellate cell; aHSCs) expressing smooth muscle α-actin (αSMA) ... ...

Abstract	Background and aims: During liver injury, quiescent hepatic stellate cells (qHSCs) transdifferentiate into proliferative and fibrogenic activated myofibroblastic phenotype (activated hepatic stellate cell; aHSCs) expressing smooth muscle α-actin (αSMA) and platelet-derived growth factor beta receptor (PDGFβR). Their interactions with gut-derived bacterial lipopolysaccharide (LPS) are implicated in hepatic fibrogenesis. However, LPS can also attenuate fibrogenic characteristics of aHSCs. Approach and results: We examined molecular mechanisms of antifibrogenic effects of LPS on aHSCs in vitro and in vivo. Culture-activated rat HSCs were exposed to 0-100 ng/mL of LPS or its active component, diphosphoryl-lipid A (DPLA), and parameters of fibrosis and inflammatory cytokines/chemokines were determined by qRT-PCR, western, and immunohistochemical analyses. In vivo, HSCs were activated by repeated CCl Conclusions: In conclusion, LPS induces a unique phenotype in aHSCs associated with down-regulation of key fibrogenic mechanisms and thus may have an important role in limiting fibrosis.
MeSH term(s)	Animals ; CCAAT-Enhancer-Binding Protein-delta/metabolism ; Carbon Tetrachloride/administration & dosage ; Carbon Tetrachloride/toxicity ; Cell Transdifferentiation/immunology ; Cells, Cultured ; Cytokines/genetics ; Cytokines/immunology ; Down-Regulation ; Gene Expression Regulation/immunology ; Gene Silencing ; Hepatic Stellate Cells/immunology ; Hepatic Stellate Cells/pathology ; Humans ; Lipid A/analogs & derivatives ; Lipid A/immunology ; Lipid A/metabolism ; Liver/cytology ; Liver/immunology ; Liver/pathology ; Liver Cirrhosis, Experimental/chemically induced ; Liver Cirrhosis, Experimental/immunology ; Liver Cirrhosis, Experimental/pathology ; Mice ; Mice, Knockout ; Myofibroblasts/immunology ; Myofibroblasts/pathology ; Oxidoreductases Acting on Sulfur Group Donors/genetics ; Primary Cell Culture ; Proto-Oncogene Proteins c-myb/metabolism ; Rats ; Signal Transduction/genetics ; Signal Transduction/immunology ; Smad7 Protein/genetics ; Smad7 Protein/metabolism ; Up-Regulation/immunology
Chemical Substances	Cebpd protein, rat ; Cytokines ; Lipid A ; Proto-Oncogene Proteins c-myb ; Smad7 Protein ; Smad7 protein, mouse ; Smad7 protein, rat ; diphosphoryl lipid A ; CCAAT-Enhancer-Binding Protein-delta (142662-43-9) ; Carbon Tetrachloride (CL2T97X0V0) ; Oxidoreductases Acting on Sulfur Group Donors (EC 1.8.-) ; GFER protein, mouse (EC 1.8.3.-)
Language	English
Publishing date	2020-10-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.31188
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Article ; Online: Clearing for Deep Tissue Imaging.

Muntifering, Michael / Castranova, Daniel / Gibson, Gregory A / Meyer, Evan / Kofron, Matthew / Watson, Alan M

Current protocols in cytometry

2018 Volume 86, Issue 1, Page(s) e38

Abstract: Biologic tissues are generally opaque due to optical properties that result in scattering and absorption of light. Preparation of tissues for optical microscopy often involves sectioning to a thickness of 50-100 µm, the practical limits of light ... ...

Abstract	Biologic tissues are generally opaque due to optical properties that result in scattering and absorption of light. Preparation of tissues for optical microscopy often involves sectioning to a thickness of 50-100 µm, the practical limits of light penetration and recovery. A researcher who wishes to image a whole tissue must acquire potentially hundreds of individual sections before rendering them into a three-dimensional volume. Clearing removes strongly light-scattering and light-absorbing components of a tissue and equalizes the refractive index of the imaging medium to that of the tissue. After clearing, the maximum depth of imaging is often defined by the microscope optics rather than the tissue. Such visibility enables the interrogation of whole tissues and even animals without the need to section. Researchers can study a biological process in the context of its three-dimensional environment, identify rare events in large volumes of tissues, and trace cells and cell-cell interactions over large distances. This article describes four popular clearing protocols that are relevant to a wide variety of scenarios across biologic disciplines: CUBIC, CLARITY, 3DISCO, and SeeDB. © 2018 by John Wiley & Sons, Inc.
MeSH term(s)	Animals ; Decision Trees ; Fluorescence ; Imaging, Three-Dimensional/methods ; Mice ; Solvents ; Staining and Labeling
Chemical Substances	Solvents
Language	English
Publishing date	2018-07-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ISSN	1934-9300
ISSN (online)	1934-9300
DOI	10.1002/cpcy.38
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Article ; Online: Two-color fluorescent in situ hybridization using chromogenic substrates in zebrafish.

Schumacher, Jennifer A / Zhao, Emma J / Kofron, Matthew J / Sumanas, Saulius

BioTechniques

2014 Volume 57, Issue 5, Page(s) 254–256

Abstract: Two-color fluorescent in situ hybridization (FISH) is a widely used technique for comparing relative gene expression patterns. Current two-color FISH protocols are not ideal for detecting weakly expressed transcripts or monitoring signal strength and ... ...

Abstract	Two-color fluorescent in situ hybridization (FISH) is a widely used technique for comparing relative gene expression patterns. Current two-color FISH protocols are not ideal for detecting weakly expressed transcripts or monitoring signal strength and background levels during the course of the reaction. Here we describe an improved FISH protocol using the conventional highly sensitive chromogenic substrates nitro blue tetrazolium (NBT)/5-bromo-4-chloro-3-indolyl phosphate (BCIP) and Vector Red in zebrafish embryos. This protocol substantially improves on existing FISH techniques by combining the advantages of long reactivity of alkaline phosphatase, chromogenic monitoring of both developing reactions, and the ability to perform subsequent high-resolution fluorescent imaging. Although tested in zebrafish, a similar approach is expected to be applicable to ISH in any model organism.
MeSH term(s)	Animals ; Chromogenic Compounds/analysis ; Embryo, Nonmammalian/chemistry ; Embryo, Nonmammalian/cytology ; Embryo, Nonmammalian/embryology ; In Situ Hybridization, Fluorescence/methods ; Microscopy, Fluorescence, Multiphoton/methods ; Zebrafish
Chemical Substances	Chromogenic Compounds
Language	English
Publishing date	2014-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	48453-2
ISSN	1940-9818 ; 0736-6205
ISSN (online)	1940-9818
ISSN	0736-6205
DOI	10.2144/000114229
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Zs.A 2435: Show issues

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Article ; Online: Nodal signalling in Xenopus: the role of Xnr5 in left/right asymmetry and heart development.

Tadjuidje, Emmanuel / Kofron, Matthew / Mir, Adnan / Wylie, Christopher / Heasman, Janet / Cha, Sang-Wook

Open biology

2016 Volume 6, Issue 8

Abstract: Nodal class TGF-β signalling molecules play essential roles in establishing the vertebrate body plan. In all vertebrates, nodal family members have specific waves of expression required for tissue specification and axis formation. In Xenopus laevis, six ... ...

Abstract	Nodal class TGF-β signalling molecules play essential roles in establishing the vertebrate body plan. In all vertebrates, nodal family members have specific waves of expression required for tissue specification and axis formation. In Xenopus laevis, six nodal genes are expressed before gastrulation, raising the question of whether they have specific roles or act redundantly with each other. Here, we examine the role of Xnr5. We find it acts at the late blastula stage as a mesoderm inducer and repressor of ectodermal gene expression, a role it shares with Vg1. However, unlike Vg1, Xnr5 depletion reduces the expression of the nodal family member xnr1 at the gastrula stage. It is also required for left/right laterality by controlling the expression of the laterality genes xnr1, antivin (lefty) and pitx2 at the tailbud stage. In Xnr5-depleted embryos, the heart field is established normally, but symmetrical reduction in Xnr5 levels causes a severely stunted midline heart, first evidenced by a reduction in cardiac troponin mRNA levels, while left-sided reduction leads to randomization of the left/right axis. This work identifies Xnr5 as the earliest step in the signalling pathway establishing normal heart laterality in Xenopus.
MeSH term(s)	Animals ; Blastula/metabolism ; Body Patterning ; Gene Expression Regulation, Developmental ; Heart/growth & development ; Left-Right Determination Factors/metabolism ; Nodal Signaling Ligands/genetics ; Nodal Signaling Ligands/metabolism ; Signal Transduction ; Transcription Factors/metabolism ; Xenopus Proteins/genetics ; Xenopus Proteins/metabolism ; Xenopus laevis/embryology ; Xenopus laevis/genetics ; Xenopus laevis/metabolism
Chemical Substances	Left-Right Determination Factors ; Nodal Signaling Ligands ; Transcription Factors ; Xenopus Proteins ; nodal1 protein, Xenopus ; nodal5 protein, Xenopus
Language	English
Publishing date	2016-08-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2630944-0
ISSN	2046-2441 ; 2046-2441
ISSN (online)	2046-2441
ISSN	2046-2441
DOI	10.1098/rsob.150187
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Article ; Online: Human stomach-on-a-chip with luminal flow and peristaltic-like motility.

Lee, Kang Kug / McCauley, Heather A / Broda, Taylor R / Kofron, Matthew J / Wells, James M / Hong, Christian I

Lab on a chip

2018 Volume 18, Issue 20, Page(s) 3079–3085

Abstract: Current in vitro approaches and animal models have critical limitations for modeling human gastrointestinal diseases because they may not properly represent multicellular human primary tissues. Therefore, there is a need for model platforms that ... ...

Abstract	Current in vitro approaches and animal models have critical limitations for modeling human gastrointestinal diseases because they may not properly represent multicellular human primary tissues. Therefore, there is a need for model platforms that recapitulate human in vivo development, physiology, and disease processes to validate new therapeutics. One of the major steps toward this goal was the generation of three-dimensional (3D) human gastric organoids (hGOs) via the directed differentiation of human pluripotent stem cells (hPSCs). The normal functions and diseases of the stomach occur in the luminal epithelium, however accessing the epithelium on the inside of organoids is challenging. We sought to develop a bioengineered platform to introduce luminal flow through hGOs to better model in vivo gastric functions. Here, we report an innovative microfluidic imaging platform housing hGOs with peristaltic luminal flow in vitro. This human stomach-on-a-chip allows robust, long-term, 3D growth of hGOs with the capacity for luminal delivery via a peristaltic pump. Organoids were cannulated and medium containing fluorescent dextran was delivered through the lumen using a peristaltic pump. This system also allowed us to rhythmically introduce stretch and contraction to the organoid, reminiscent of gastric motility. Our platform has the potential for long-term delivery of nutrients or pharmacological agents into the gastric lumen in vitro for the study of human gastric physiology, disease modeling, and drug screening, among other possibilities.
MeSH term(s)	Gastrointestinal Motility ; Humans ; Organoids/cytology ; Stomach/cytology ; Stomach/physiology ; Tissue Array Analysis/instrumentation ; Tissue Array Analysis/methods
Language	English
Publishing date	2018-09-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2056646-3
ISSN	1473-0189 ; 1473-0197
ISSN (online)	1473-0189
ISSN	1473-0197
DOI	10.1039/c8lc00910d
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Article ; Online: Asymmetrically Segregated Mitochondria Provide Cellular Memory of Hematopoietic Stem Cell Replicative History and Drive HSC Attrition.

Hinge, Ashwini / He, Jingyi / Bartram, James / Javier, Jose / Xu, Juying / Fjellman, Ellen / Sesaki, Hiromi / Li, Tingyu / Yu, Jie / Wunderlich, Mark / Mulloy, James / Kofron, Matthew / Salomonis, Nathan / Grimes, H Leighton / Filippi, Marie-Dominique

Cell stem cell

2020 Volume 26, Issue 3, Page(s) 420–430.e6

Abstract: The metabolic requirements of hematopoietic stem cells (HSCs) change with their cell cycle activity. However, the underlying role of mitochondria remains ill-defined. Here we found that, after mitochondrial activation with replication, HSCs irreversibly ... ...

Abstract	The metabolic requirements of hematopoietic stem cells (HSCs) change with their cell cycle activity. However, the underlying role of mitochondria remains ill-defined. Here we found that, after mitochondrial activation with replication, HSCs irreversibly remodel the mitochondrial network and that this network is not repaired after HSC re-entry into quiescence, contrary to hematopoietic progenitors. HSCs keep and accumulate dysfunctional mitochondria through asymmetric segregation during active division. Mechanistically, mitochondria aggregate and depolarize after stress because of loss of activity of the mitochondrial fission regulator Drp1 onto mitochondria. Genetic and pharmacological studies indicate that inactivation of Drp1 causes loss of HSC regenerative potential while maintaining HSC quiescence. Molecularly, HSCs carrying dysfunctional mitochondria can re-enter quiescence but fail to synchronize the transcriptional control of core cell cycle and metabolic components in subsequent division. Thus, loss of fidelity of mitochondrial morphology and segregation is one type of HSC divisional memory and drives HSC attrition.
MeSH term(s)	Cell Cycle ; Cell Division ; Cell Self Renewal ; Hematopoietic Stem Cells/metabolism ; Mitochondria
Language	English
Publishing date	2020-02-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2375354-7
ISSN	1875-9777 ; 1934-5909
ISSN (online)	1875-9777
ISSN	1934-5909
DOI	10.1016/j.stem.2020.01.016
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Zs.A 6589: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Patient-Derived Organotypic Epithelial Rafts Model Phenotypes in Juvenile-Onset Recurrent Respiratory Papillomatosis.

Bedard, Mary C / Brusadelli, Marion G / Carlile, Adrean / Ruiz-Torres, Sonya / Lodin, Hannah / Lee, Denis / Kofron, Matthew / Lambert, Paul F / Lane, Adam / Ameziane, Najim / Bahassi, El Mustapha / Wikenheiser-Brokamp, Kathryn A / de Alarcon, Alessandro / Smith, David F / Wells, Susanne I

Viruses

2021 Volume 13, Issue 1

Abstract: Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is driven by human papillomavirus (HPV) low-risk strains and is associated with significant morbidity. While previous studies of 2D cultures have shed light on disease pathogenesis and ... ...

Abstract	Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is driven by human papillomavirus (HPV) low-risk strains and is associated with significant morbidity. While previous studies of 2D cultures have shed light on disease pathogenesis and demonstrated the utility of personalized medicine approaches, monolayer cultures lack the 3D tissue architecture and physiology of stratified, sequentially differentiated mucosal epithelium important in RRP disease pathogenesis. Herein we describe the establishment of JoRRP-derived primary cell populations that retain HPV genomes and viral gene expression in culture. These were directly compared to cells from matched adjacent non-diseased tissue, given the known RRP patient-to-patient variability. JoRRP papilloma versus control cells displayed decreased growth at subconfluency, with a switch to increased growth after reaching confluency, suggesting relative resistance to cell-cell contact and/or differentiation. The same papilloma cells grown as 3D organotypic rafts harbored hyperproliferation as compared to controls, with increased numbers of proliferating basal cells and inappropriately replicating suprabasal cells, mimicking phenotypes in the patient biopsies from which they were derived. These complementary model systems provide novel opportunities to elucidate disease mechanisms at distinct stages in JoRRP progression and to identify diagnostic, prognostic and therapeutic factors to personalize patient management and treatment.
MeSH term(s)	Alphapapillomavirus/genetics ; Alphapapillomavirus/isolation & purification ; Epithelial Cells/virology ; Humans ; Organ Culture Techniques ; Papillomavirus Infections/pathology ; Papillomavirus Infections/virology ; Phenotype ; RNA, Viral/genetics ; Real-Time Polymerase Chain Reaction ; Respiratory Tract Infections/pathology ; Respiratory Tract Infections/virology ; Risk Factors
Chemical Substances	RNA, Viral
Language	English
Publishing date	2021-01-06
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13010068
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