29037
2022
eng
20
11
article
1
--
2022-10-19
--
A human stem cell-derived brain-liver chip for assessing blood-brain-barrier permeation of pharmaceutical drugs
Significant advancements in the field of preclinical in vitro blood-brain barrier (BBB) models have been achieved in recent years, by developing monolayer-based culture systems towards complex multi-cellular assays. The coupling of those models with other relevant organoid systems to integrate the investigation of blood-brain barrier permeation in the larger picture of drug distribution and metabolization is still missing. Here, we report for the first time the combination of a human induced pluripotent stem cell (hiPSC)-derived blood-brain barrier model with a cortical brain and a liver spheroid model from the same donor in a closed microfluidic system (MPS). The two model compounds atenolol and propranolol were used to measure permeation at the blood–brain barrier and to assess metabolization. Both substances showed an in vivo-like permeation behavior and were metabolized in vitro. Therefore, the novel multi-organ system enabled not only the measurement of parent compound concentrations but also of metabolite distribution at the blood-brain barrier.
Cells
2073-4409
10.3390/cells11203295
urn:nbn:de:bvb:20-opus-290375
2022-11-04T10:55:15+00:00
sword
swordwue
attachment; filename=deposit.zip
5ce4e704914e2993e3653d29386c7d5f
Cells (2022) 11:20, 3295. https://doi.org/10.3390/cells11203295
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Leopold Koenig
Anja Patricia Ramme
Daniel Faust
Manuela Mayer
Tobias Flötke
Anna Gerhartl
Andreas Brachner
Winfried Neuhaus
Antje Appelt-Menzel
Marco Metzger
Uwe Marx
Eva-Maria Dehne
eng
uncontrolled
blood-brain barrier (BBB) model
eng
uncontrolled
human induced pluripotent stem cells (hiPSCs)
eng
uncontrolled
microphysiological systems (MPS)
eng
uncontrolled
multi-organ chip
eng
uncontrolled
brain–liver chip
Biowissenschaften; Biologie
Medizin und Gesundheit
open_access
Lehrstuhl für Tissue Engineering und Regenerative Medizin
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/29037/cells-11-03295-v2.pdf
35045
2023
eng
1
15
article
1
--
--
--
A primary cell-based in vitro model of the human small intestine reveals host olfactomedin 4 induction in response to Salmonella Typhimurium infection
Infection research largely relies on classical cell culture or mouse models. Despite having delivered invaluable insights into host-pathogen interactions, both have limitations in translating mechanistic principles to human pathologies. Alternatives can be derived from modern Tissue Engineering approaches, allowing the reconstruction of functional tissue models in vitro. Here, we combined a biological extracellular matrix with primary tissue-derived enteroids to establish an in vitro model of the human small intestinal epithelium exhibiting in vivo-like characteristics. Using the foodborne pathogen Salmonella enterica serovar Typhimurium, we demonstrated the applicability of our model to enteric infection research in the human context. Infection assays coupled to spatio-temporal readouts recapitulated the established key steps of epithelial infection by this pathogen in our model. Besides, we detected the upregulation of olfactomedin 4 in infected cells, a hitherto unrecognized aspect of the host response to Salmonella infection. Together, this primary human small intestinal tissue model fills the gap between simplistic cell culture and animal models of infection, and shall prove valuable in uncovering human-specific features of host-pathogen interplay.
Gut Microbes
10.1080/19490976.2023.2186109
urn:nbn:de:bvb:20-opus-350451
@articleDaullary.2023, author = Däullary, Thomas and Imdahl, Fabian and Dietrich, Oliver and Hepp, Laura and Krammer, Tobias and Fey, Christina and Neuhaus, Winfried and Metzger, Marco and Vogel, Jörg and Westermann, Alexander J. and Saliba, Antoine-Emmanuel and Zdzieblo, Daniela, year = 2023, title = A primary cell-based invitro model of the human small intestine reveals host olfactomedin 4 induction in response to Salmonella Typhimurium infection, pages = 2186109, volume = 15, number = 1, journal = Gut microbes, doi = 10.1080/19490976.2023.2186109
md5:b95e97262f4361436df5dc589ef8c15b
2024-02-22T06:45:04+00:00
/tmp/phpXbR7n5
bibtex
65d6ed7099a802.27721416
Gut Microbes (2023) 15:1, 2186109. DOI: 10.1080/19490976.2023.2186109
false
true
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Thomas Däullary
Fabian Imdahl
Oliver Dietrich
Laura Hepp
Tobias Krammer
Christina Fey
Winfried Neuhaus
Marco Metzger
Jörg Vogel
Alexander J. Westermann
Antoine-Emmanuel Saliba
Daniela Zdzieblo
eng
uncontrolled
intestinal enteroids
eng
uncontrolled
biological scaffold
eng
uncontrolled
Salmonella Typhimurium
eng
uncontrolled
OLFM4
eng
uncontrolled
NOTCH
eng
uncontrolled
filamentous Salmonella Typhimurium
eng
uncontrolled
bacterial migration
eng
uncontrolled
bacterial virulence
eng
uncontrolled
3D tissue model
eng
uncontrolled
olfactomedin 4
eng
uncontrolled
infection
Medizin und Gesundheit
open_access
Institut für Molekulare Infektionsbiologie
Theodor-Boveri-Institut für Biowissenschaften
Lehrstuhl für Tissue Engineering und Regenerative Medizin
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/35045/Daeullary_Gut_Microbes_2023.pdf
22945
2020
eng
2
16
article
1
2021-03-04
--
--
A three-dimensional intestinal tissue model reveals factors and small regulatory RNAs important for colonization with Campylobacter jejuni
The Gram-negative Epsilonproteobacterium Campylobacter jejuni is currently the most prevalent bacterial foodborne pathogen. Like for many other human pathogens, infection studies with C. jejuni mainly employ artificial animal or cell culture models that can be limited in their ability to reflect the in-vivo environment within the human host. Here, we report the development and application of a human three-dimensional (3D) infection model based on tissue engineering to study host-pathogen interactions. Our intestinal 3D tissue model is built on a decellularized extracellular matrix scaffold, which is reseeded with human Caco-2 cells. Dynamic culture conditions enable the formation of a polarized mucosal epithelial barrier reminiscent of the 3D microarchitecture of the human small intestine. Infection with C. jejuni demonstrates that the 3D tissue model can reveal isolate-dependent colonization and barrier disruption phenotypes accompanied by perturbed localization of cell-cell junctions. Pathogenesis-related phenotypes of C. jejuni mutant strains in the 3D model deviated from those obtained with 2D-monolayers, but recapitulated phenotypes previously observed in animal models. Moreover, we demonstrate the involvement of a small regulatory RNA pair, CJnc180/190, during infections and observe different phenotypes of CJnc180/190 mutant strains in 2D vs. 3D infection models. Hereby, the CJnc190 sRNA exerts its pathogenic influence, at least in part, via repression of PtmG, which is involved in flagellin modification. Our results suggest that the Caco-2 cell-based 3D tissue model is a valuable and biologically relevant tool between in-vitro and in-vivo infection models to study virulence of C. jejuni and other gastrointestinal pathogens.
PLoS Pathogens
10.1371/journal.ppat.1008304
urn:nbn:de:bvb:20-opus-229454
publish
PLoS Pathog 16(2): e1008304. https://doi.org/10.1371/ journal.ppat.1008304
true
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Mona Alzheimer
Sarah L. Svensson
Fabian König
Matthias Schweinlin
Marco Metzger
Heike Walles
Cynthia M. Sharma
eng
uncontrolled
in vitro
eng
uncontrolled
stem cells
eng
uncontrolled
invasion
eng
uncontrolled
host
eng
uncontrolled
adhesion
eng
uncontrolled
epithelial cells
eng
uncontrolled
translocation
eng
uncontrolled
virulence
eng
uncontrolled
responses
eng
uncontrolled
microenvironment
Medizin und Gesundheit
open_access
Institut für Molekulare Infektionsbiologie
Lehrstuhl für Tissue Engineering und Regenerative Medizin
Förderzeitraum 2020
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/22945/ppat.1008304.pdf
14654
2016
eng
e0151335
3
11
article
1
2017-03-31
--
--
Activation of Myenteric Glia during Acute Inflammation In Vitro and In Vivo
Background
Enteric glial cells (EGCs) are the main constituent of the enteric nervous system and share similarities with astrocytes from the central nervous system including their reactivity to an inflammatory microenvironment. Previous studies on EGC pathophysiology have specifically focused on mucosal glia activation and its contribution to mucosal inflammatory processes observed in the gut of inflammatory bowel disease (IBD) patients. In contrast knowledge is scarce on intestinal inflammation not locally restricted to the mucosa but systemically affecting the intestine and its effect on the overall EGC network.
Methods and Results
In this study, we analyzed the biological effects of a systemic LPS-induced hyperinflammatory insult on overall EGCs in a rat model in vivo, mimicking the clinical situation of systemic inflammation response syndrome (SIRS). Tissues from small and large intestine were removed 4 hours after systemic LPS-injection and analyzed on transcript and protein level. Laser capture microdissection was performed to study plexus-specific gene expression alterations. Upon systemic LPS-injection in vivo we observed a rapid and dramatic activation of Glial Fibrillary Acidic Protein (GFAP)-expressing glia on mRNA level, locally restricted to the myenteric plexus. To study the specific role of the GFAP subpopulation, we established flow cytometry-purified primary glial cell cultures from GFAP promotor-driven EGFP reporter mice. After LPS stimulation, we analyzed cytokine secretion and global gene expression profiles, which were finally implemented in a bioinformatic comparative transcriptome analysis. Enriched GFAP+ glial cells cultured as gliospheres secreted increased levels of prominent inflammatory cytokines upon LPS stimulation. Additionally, a shift in myenteric glial gene expression profile was induced that predominantly affected genes associated with immune response.
Conclusion and Significance
Our findings identify the myenteric GFAP-expressing glial subpopulation as particularly susceptible and responsive to acute systemic inflammation of the gut wall and complement knowledge on glial involvement in mucosal inflammation of the intestine.
PLoS One
10.1371/journal.pone.0151335
urn:nbn:de:bvb:20-opus-146544
PLoS ONE 11(3): e0151335. doi:10.1371/journal.pone.0151335
Corinna Rosenbaum
Martin Alexander Schick
Jakob Wollborn
Andreas Heider
Claus-Jürgen Scholz
Alexander Cecil
Beate Niesler
Johannes Hirrlinger
Heike Walles
Marco Metzger
eng
uncontrolled
gene expression
eng
uncontrolled
gastrointestinal tract
eng
uncontrolled
inflammatory bowel disease
eng
uncontrolled
central nervous system
eng
uncontrolled
systemic inflammatory response syndrome
eng
uncontrolled
inflammation
eng
uncontrolled
astrocytes
eng
uncontrolled
cytokines
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Anästhesiologie (ab 2004)
Theodor-Boveri-Institut für Biowissenschaften
Lehrstuhl für Tissue Engineering und Regenerative Medizin
Förderzeitraum 2016
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14654/Rosenbaum_journal.pone.0151335.pdf
11830
2014
eng
276
6
article
1
2015-08-21
--
--
Age-related gene expression analysis in enteric ganglia of human colon after laser microdissection
The enteric nervous system (ENS) poses the intrinsic innervation of the gastrointestinal tract and plays a critical role for all stages of postnatal life. There is increasing scientific and clinical interest in acquired or age-related gastrointestinal dysfunctions that can be manifested in diseases such as gut constipation or fecal incontinence. In this study, we sought to analyze age-dependent changes in the gene expression profile of the human ENS, particularly in the myenteric plexus. Therefore, we used the laser microdissection technique which has been proven as a feasible tool to analyze distinct cell populations within heterogeneously composed tissues. Full biopsy gut samples were prepared from children (4–12 months), middle aged (48–58 years) and aged donors (70–95 years). Cryosections were histologically stained with H&E, the ganglia of the myenteric plexus identified and RNA isolated using laser microdissection technique. Quantitative PCR was performed for selected neural genes, neurotransmitters and receptors. Data were confirmed on protein level using NADPH-diaphorase staining and immunohistochemistry. As result, we demonstrate age-associated alterations in site-specific gene expression pattern of the ENS. Thus, in the adult and aged distal parts of the colon a marked decrease in relative gene expression of neural key genes like NGFR, RET, NOS1 and a concurrent increase of CHAT were observed. Further, we detected notable regional differences of RET, CHAT, TH, and S100B comparing gene expression in aged proximal and distal colon. Interestingly, markers indicating cellular senescence or oxidative stress (SNCA, CASP3, CAT, SOD2, and TERT) were largely unchanged within the ENS. For the first time, our study also describes the age-dependent expression pattern of all major sodium channels within the ENS. Our results are in line with previous studies showing spatio-temporal differences within the mammalian ENS.
Frontiers in Aging Neuroscience
10.3389/fnagi.2014.00276
1663-4365
urn:nbn:de:bvb:20-opus-118308
Frontiers in Aging Neuroscience 6:276. doi:10.3389/fnagi.2014.00276
Susan Hetz
Ali Acikgoez
Corinna Moll
Heinz-Georg Jahnke
Andrea A. Robitzki
Roman Metzger
Marco Metzger
eng
uncontrolled
enteric nervous system
eng
uncontrolled
myenteric plexus
eng
uncontrolled
aging
eng
uncontrolled
sodium channels
eng
uncontrolled
laser microdissection
Medizin und Gesundheit
open_access
Lehrstuhl für Tissue Engineering und Regenerative Medizin
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11830/018_Hetz_Frontiers_in_aging_neuroscience.pdf
22942
2020
eng
1
11, 2020
article
1
2021-03-04
--
--
An Advanced Human Intestinal Coculture Model Reveals Compartmentalized Host and Pathogen Strategies during Salmonella Infection
A major obstacle in infection biology is the limited ability to recapitulate human disease trajectories in traditional cell culture and animal models, which impedes the translation of basic research into clinics. Here, we introduce a three-dimensional (3D) intestinal tissue model to study human enteric infections at a level of detail that is not achieved by conventional two-dimensional monocultures. Our model comprises epithelial and endothelial layers, a primary intestinal collagen scaffold, and immune cells. Upon Salmonella infection, the model mimics human gastroenteritis, in that it restricts the pathogen to the epithelial compartment, an advantage over existing mouse models. Application of dual transcriptome sequencing to the Salmonella-infected model revealed the communication of epithelial, endothelial, monocytic, and natural killer cells among each other and with the pathogen. Our results suggest that Salmonella uses its type III secretion systems to manipulate STAT3-dependent inflammatory responses locally in the epithelium without accompanying alterations in the endothelial compartment. Our approach promises to reveal further human-specific infection strategies employed by Salmonella and other pathogens.
IMPORTANCE Infection research routinely employs in vitro cell cultures or in vivo mouse models as surrogates of human hosts. Differences between murine and human immunity and the low level of complexity of traditional cell cultures, however, highlight the demand for alternative models that combine the in vivo-like properties of the human system with straightforward experimental perturbation. Here, we introduce a 3D tissue model comprising multiple cell types of the human intestinal barrier, a primary site of pathogen attack. During infection with the foodborne pathogen Salmonella enterica serovar Typhimurium, our model recapitulates human disease aspects, including pathogen restriction to the epithelial compartment, thereby deviating from the systemic infection in mice. Combination of our model with state-of-the-art genetics revealed Salmonella-mediated local manipulations of human immune responses, likely contributing to the establishment of the pathogen's infection niche. We propose the adoption of similar 3D tissue models to infection biology, to advance our understanding of molecular infection strategies employed by bacterial pathogens in their human host.
mBio
10.1128/mBio.03348-19
urn:nbn:de:bvb:20-opus-229428
publish
mBio 11:e03348-19. https://doi.org/ 10.1128/mBio.03348-19.
true
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Leon N. Schulte
Matthias Schweinlin
Alexander J. Westermann
Harshavardhan Janga
Sara C. Santos
Silke Appenzeller
Heike Walles
Jörg Vogel
Marco Metzger
eng
uncontrolled
Salmonella
eng
uncontrolled
gene expression
eng
uncontrolled
infectious disease
Medizin und Gesundheit
open_access
Institut für Molekulare Infektionsbiologie
Lehrstuhl für Tissue Engineering und Regenerative Medizin
Förderzeitraum 2020
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/22942/mBio-2020-Schulte-e03348-19.full.pdf
17065
2017
eng
1484–1493
8
article
1
2018-10-30
--
--
Calcium fluoride based multifunctional nanoparticles for multimodal imaging
New multifunctional nanoparticles (NPs) that can be used as contrast agents (CA) in different imaging techniques, such as photoluminescence (PL) microscopy and magnetic resonance imaging (MRI), open new possibilities for medical imaging, e.g., in the fields of diagnostics or tissue characterization in regenerative medicine. The focus of this study is on the synthesis and characterization of CaF\(_{2}\):(Tb\(^{3+}\),Gd\(^{3+}\)) NPs. Fabricated in a wet-chemical procedure, the spherical NPs with a diameter of 5–10 nm show a crystalline structure. Simultaneous doping of the NPs with different lanthanide ions, leading to paramagnetism and fluorescence, makes them suitable for MR and PL imaging. Owing to the Gd\(^{3+}\) ions on the surface, the NPs reduce the MR T\(_{1}\) relaxation time constant as a function of their concentration. Thus, the NPs can be used as a MRI CA with a mean relaxivity of about r = 0.471 mL·mg\(^{−1}\)·s\(^{−1}\). Repeated MRI examinations of four different batches prove the reproducibility of the NP synthesis and determine the long-term stability of the CAs. No cytotoxicity of NP concentrations between 0.5 and 1 mg·mL\(^{−1}\) was observed after exposure to human dermal fibroblasts over 24 h. Overall this study shows, that the CaF\(_{2}\):(Tb\(^{3+}\),Gd\(^{3+}\)) NPs are suitable for medical imaging.
Beilstein Journal of Nanotechnology
10.3762/bjnano.8.148
28900602
urn:nbn:de:bvb:20-opus-170657
Beilstein Journal of Nanotechnology 2017, 8, 1484-1493. DOI: 10.3762/bjnano.8.148
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Marion Straßer
Joachim H. X. Schrauth
Sofia Dembski
Daniel Haddad
Bernd Ahrens
Stefan Schweizer
Bastian Christ
Alevtina Cubukova
Marco Metzger
Heike Walles
Peter M. Jakob
Gerhard Sextl
eng
uncontrolled
calcium fluoride nanoparticles
eng
uncontrolled
magnetic resonance imaging (MRI)
eng
uncontrolled
multifunctional nanoparticles
eng
uncontrolled
multimodal imaging
eng
uncontrolled
photoluminescence
Chemie und zugeordnete Wissenschaften
open_access
Physikalisches Institut
Institut für Funktionsmaterialien und Biofabrikation
Lehrstuhl für Tissue Engineering und Regenerative Medizin
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17065/053_Strasser_BEILSTEIN-JOURNAL-OF-NANOTECHNOLOGY.pdf
11428
2014
eng
3087 - 3096
10
article
1
2015-06-10
--
--
Conjugates of methylated cyclodextrin derivatives and hydroxyethyl starch (HES): Synthesis, cytotoxicity and inclusion of anaesthetic actives
The mono-6-deoxy-6-azides of 2,6-di-O-methyl-beta-cyclodextrin (DIMEB) and randomly methylated-beta-cyclodextrin (RAMEB) were conjugated to propargylated hydroxyethyl starch (HES) by Cu+-catalysed [2 + 3] cycloaddition. The resulting water soluble polymers showed lower critical solution temperatures (LCST) at 52.5 degrees C (DIMEB-HES) and 84.5 degrees C (RAMEB-HES), respectively. LCST phase separations could be completely avoided by the introduction of a small amount of carboxylate groups at the HES backbone. The methylated CDs conjugated to the HES backbone exhibited significantly lower cytotoxicities than the corresponding monomeric CD derivatives. Since the binding potentials of these CD conjugates were very high, they are promising candidates for new oral dosage forms of anaesthetic actives.
Beilstein Journal of Organic Chemistry
10.3762/bjoc.10.325
1860-5397
25670977
urn:nbn:de:bvb:20-opus-114280
Beilstein Journal of Organic Chemistry 2014, 10, 3087–3096. doi:10.3762/bjoc.10.325
Lisa Markenstein
Antje Appelt-Menzel
Marco Metzger
Gerhard Wenz
eng
uncontrolled
midazolam
eng
uncontrolled
supermolecular carrier systems
eng
uncontrolled
beta-cyclodextrin
eng
uncontrolled
pharmaceutical applications
eng
uncontrolled
gamma-cyclodextrin
eng
uncontrolled
anaesthetics
eng
uncontrolled
complexation
eng
uncontrolled
cyclodextrin
eng
uncontrolled
LCST
eng
uncontrolled
lower critical solution temperature
eng
uncontrolled
acid dissociation
eng
uncontrolled
drug
eng
uncontrolled
rat
eng
uncontrolled
cycloaddition
eng
uncontrolled
occupancy
eng
uncontrolled
polymer
eng
uncontrolled
sevoflurane
eng
uncontrolled
solubility
eng
uncontrolled
starch
Medizin und Gesundheit
open_access
Lehrstuhl für Tissue Engineering und Regenerative Medizin
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11428/004_Markenstein_Beilstein_Journal_of_Organic_Chemistry.pdf
17098
2017
eng
894-906
4
8
article
1
2018-11-02
--
--
Establishment of a Human Blood-Brain Barrier Co-culture Model Mimicking the Neurovascular Unit Using Induced Pluri- and Multipotent Stem Cells
In vitro models of the human blood-brain barrier (BBB) are highly desirable for drug development. This study aims to analyze a set of ten different BBB culture models based on primary cells, human induced pluripotent stem cells (hiPSCs), and multipotent fetal neural stem cells (fNSCs). We systematically investigated the impact of astrocytes, pericytes, and NSCs on hiPSC-derived BBB endothelial cell function and gene expression. The quadruple culture models, based on these four cell types, achieved BBB characteristics including transendothelial electrical resistance (TEER) up to 2,500 Ω cm\(^{2}\) and distinct upregulation of typical BBB genes. A complex in vivo-like tight junction (TJ) network was detected by freeze-fracture and transmission electron microscopy. Treatment with claudin-specific TJ modulators caused TEER decrease, confirming the relevant role of claudin subtypes for paracellular tightness. Drug permeability tests with reference substances were performed and confirmed the suitability of the models for drug transport studies.
Stem Cell Reports
10.1016/j.stemcr.2017.02.021
28344002
urn:nbn:de:bvb:20-opus-170982
Stem Cell Reports 2017, 8(4), 894-906. DOI: 10.1016/j.stemcr.2017.02.021
false
true
CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International
Antje Appelt-Menzel
Alevtina Cubukova
Katharina Günther
Frank Edenhofer
Jörg Piontek
Gerd Krause
Tanja Stüber
Heike Walles
Winfried Neuhaus
Marco Metzger
eng
uncontrolled
blood-brain barrier (BBB) model
eng
uncontrolled
human induced pluripotent stem cells (hiPSCs)human induced pluripotent stem cells (hiPSCs)
eng
uncontrolled
multipotent fetal neural stem cells (fNSCs)
eng
uncontrolled
neurovascular unit in vitro
Medizin und Gesundheit
open_access
Frauenklinik und Poliklinik
Institut für Anatomie und Zellbiologie
Lehrstuhl für Tissue Engineering und Regenerative Medizin
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17098/082_Appelt-Menzelt_STEM-CELL-RESEARCH.pdf
30131
2022
2022
eng
1
13
article
1
--
--
--
Establishment of the SIS scaffold-based 3D model of human peritoneum for studying the dissemination of ovarian cancer
Ovarian cancer is the second most common gynecological malignancy in women. More than 70% of the cases are diagnosed at the advanced stage, presenting as primary peritoneal metastasis, which results in a poor 5-year survival rate of around 40%. Mechanisms of peritoneal metastasis, including adhesion, migration, and invasion, are still not completely understood and therapeutic options are extremely limited. Therefore, there is a strong requirement for a 3D model mimicking the in vivo situation. In this study, we describe the establishment of a 3D tissue model of the human peritoneum based on decellularized porcine small intestinal submucosa (SIS) scaffold. The SIS scaffold was populated with human dermal fibroblasts, with LP-9 cells on the apical side representing the peritoneal mesothelium, while HUVEC cells on the basal side of the scaffold served to mimic the endothelial cell layer. Functional analyses of the transepithelial electrical resistance (TEER) and the FITC-dextran assay indicated the high barrier integrity of our model. The histological, immunohistochemical, and ultrastructural analyses showed the main characteristics of the site of adhesion. Initial experiments using the SKOV-3 cell line as representative for ovarian carcinoma demonstrated the usefulness of our models for studying tumor cell adhesion, as well as the effect of tumor cells on endothelial cell-to-cell contacts. Taken together, our data show that the novel peritoneal 3D tissue model is a promising tool for studying the peritoneal dissemination of ovarian cancer.
Journal of Tissue Engineering
2041-7314
10.1177/20417314221088514
urn:nbn:de:bvb:20-opus-301311
@articleHerbert.2022, author = Herbert, Saskia-Laureen and Fick, Andrea and Heydarian, Motaharehsadat and Metzger, Marco and Wöckel, Achim and Rudel, Thomas and Kozjak-Pavlovic, Vera and Wulff, Christine, year = 2022, title = Establishment of the SIS scaffold-based 3D model of human peritoneum for studying the dissemination of ovarian cancer, pages = 20417314221088514, volume = 13, issn = 2041-7314, journal = Journal of tissue engineering, doi = 10.1177/20417314221088514,
md5:32ab45e10e0618ae2222da7db364c71d
2023-01-25T15:20:43+00:00
/tmp/phpK9qWsg
bibtex
63d148cb2152f3.61730211
Journal of Tissue Engineering (2022) 13:20417314221088514. DOI: 10.1177/20417314221088514
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Saskia-Laureen Herbert
Andrea Fick
Motaharehsadat Heydarian
Marco Metzger
Achim Wöckel
Thomas Rudel
Vera Kozjak-Pavlovic
Christine Wulff
eng
uncontrolled
ovarian cancer
eng
uncontrolled
3D tissue model
eng
uncontrolled
co-culture
eng
uncontrolled
peritoneal metastasis
eng
uncontrolled
cancer dissemination
Biowissenschaften; Biologie
open_access
Frauenklinik und Poliklinik
Theodor-Boveri-Institut für Biowissenschaften
Lehrstuhl für Tissue Engineering und Regenerative Medizin
Förderzeitraum 2022
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/30131/20417314221088514.pdf