@article{SrivastavaBencurovaGuptaetal.2019,
  author    = {Srivastava, Mugdha and Bencurova, Elena and Gupta, Shishir K. and Weiss, Esther and L{\"o}ffler, J{\"u}rgen and Dandekar, Thomas},
  title     = {Aspergillus fumigatus challenged by human dendritic cells: metabolic and regulatory pathway responses testify a tight battle},
  series = {Frontiers in Cellular and Infection Microbiology},
  volume    = {9},
  journal   = {Frontiers in Cellular and Infection Microbiology},
  doi       = {10.3389/fcimb.2019.00168},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201368},
  pages     = {168},
  year      = {2019},
  abstract  = {Dendritic cells (DCs) are antigen presenting cells which serve as a passage between the innate and the acquired immunity. Aspergillosis is a major lethal condition in immunocompromised patients caused by the adaptable saprophytic fungus Aspergillus fumigatus. The healthy human immune system is capable to ward off A. fumigatus infections however immune-deficient patients are highly vulnerable to invasive aspergillosis. A. fumigatus can persist during infection due to its ability to survive the immune response of human DCs. Therefore, the study of the metabolism specific to the context of infection may allow us to gain insight into the adaptation strategies of both the pathogen and the immune cells. We established a metabolic model of A. fumigatus central metabolism during infection of DCs and calculated the metabolic pathway (elementary modes; EMs). Transcriptome data were used to identify pathways activated when A. fumigatus is challenged with DCs. In particular, amino acid metabolic pathways, alternative carbon metabolic pathways and stress regulating enzymes were found to be active. Metabolic flux modeling identified further active enzymes such as alcohol dehydrogenase, inositol oxygenase and GTP cyclohydrolase participating in different stress responses in A. fumigatus. These were further validated by qRT-PCR from RNA extracted under these different conditions. For DCs, we outlined the activation of metabolic pathways in response to the confrontation with A. fumigatus. We found the fatty acid metabolism plays a crucial role, along with other metabolic changes. The gene expression data and their analysis illuminate additional regulatory pathways activated in the DCs apart from interleukin regulation. In particular, Toll-like receptor signaling, NOD-like receptor signaling and RIG-I-like receptor signaling were active pathways. Moreover, we identified subnetworks and several novel key regulators such as UBC, EGFR, and CUL3 of DCs to be activated in response to A. fumigatus. In conclusion, we analyze the metabolic and regulatory responses of A. fumigatus and DCs when confronted with each other.},
  language  = {en}
}
@article{DjuzenovaFiedlerMemmeletal.2019,
  author    = {Djuzenova, Cholpon S. and Fiedler, Vanessa and Memmel, Simon and Katzer, Astrid and Sisario, Dmitri and Brosch, Philippa K. and G{\"o}hrung, Alexander and Frister, Svenja and Zimmermann, Heiko and Flentje, Michael and Sukhorukov, Vladimir L.},
  title     = {Differential effects of the Akt inhibitor MK-2206 on migration and radiation sensitivity of glioblastoma cells},
  series = {BMC Cancer},
  volume    = {19},
  journal   = {BMC Cancer},
  doi       = {10.1186/s12885-019-5517-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200290},
  pages     = {299},
  year      = {2019},
  abstract  = {Background Most tumor cells show aberrantly activated Akt which leads to increased cell survival and resistance to cancer radiotherapy. Therefore, targeting Akt can be a promising strategy for radiosensitization. Here, we explore the impact of the Akt inhibitor MK-2206 alone and in combination with the dual PI3K and mTOR inhibitor PI-103 on the radiation sensitivity of glioblastoma cells. In addition, we examine migration of drug-treated cells. Methods Using single-cell tracking and wound healing migration tests, colony-forming assay, Western blotting, flow cytometry and electrorotation we examined the effects of MK-2206 and PI-103 and/or irradiation on the migration, radiation sensitivity, expression of several marker proteins, DNA damage, cell cycle progression and the plasma membrane properties in two glioblastoma (DK-MG and SNB19) cell lines, previously shown to differ markedly in their migratory behavior and response to PI3K/mTOR inhibition. Results We found that MK-2206 strongly reduces the migration of DK-MG but only moderately reduces the migration of SNB19 cells. Surprisingly, MK-2206 did not cause radiosensitization, but even increased colony-forming ability after irradiation. Moreover, MK-2206 did not enhance the radiosensitizing effect of PI-103. The results appear to contradict the strong depletion of p-Akt in MK-2206-treated cells. Possible reasons for the radioresistance of MK-2206-treated cells could be unaltered or in case of SNB19 cells even increased levels of p-mTOR and p-S6, as compared to the reduced expression of these proteins in PI-103-treated samples. We also found that MK-2206 did not enhance IR-induced DNA damage, neither did it cause cell cycle distortion, nor apoptosis nor excessive autophagy. Conclusions Our study provides proof that MK-2206 can effectively inhibit the expression of Akt in two glioblastoma cell lines. However, due to an aberrant activation of mTOR in response to Akt inhibition in PTEN mutated cells, the therapeutic window needs to be carefully defined, or a combination of Akt and mTOR inhibitors should be considered.},
  language  = {en}
}
@article{SbieraKunzWeigandetal.2019,
  author    = {Sbiera, Silviu and Kunz, Meik and Weigand, Isabel and Deutschbein, Timo and Dandekar, Thomas and Fassnacht, Martin},
  title     = {The new genetic landscape of Cushing's disease: deubiquitinases in the spotlight},
  series = {Cancers},
  volume    = {11},
  journal   = {Cancers},
  number    = {11},
  issn      = {2072-6694},
  doi       = {10.3390/cancers11111761},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193194},
  pages     = {1761},
  year      = {2019},
  abstract  = {Cushing's disease (CD) is a rare condition caused by adrenocorticotropic hormone (ACTH)-producing adenomas of the pituitary, which lead to hypercortisolism that is associated with high morbidity and mortality. Treatment options in case of persistent or recurrent disease are limited, but new insights into the pathogenesis of CD are raising hope for new therapeutic avenues. Here, we have performed a meta-analysis of the available sequencing data in CD to create a comprehensive picture of CD's genetics. Our analyses clearly indicate that somatic mutations in the deubiquitinases are the key drivers in CD, namely USP8 (36.5\%) and USP48 (13.3\%). While in USP48 only Met415 is affected by mutations, in USP8 there are 26 different mutations described. However, these different mutations are clustering in the same hotspot region (affecting in 94.5\% of cases Ser718 and Pro720). In contrast, pathogenic variants classically associated with tumorigenesis in genes like TP53 and BRAF are also present in CD but with low incidence (12.5\% and 7\%). Importantly, several of these mutations might have therapeutic potential as there are drugs already investigated in preclinical and clinical setting for other diseases. Furthermore, network and pathway analyses of all somatic mutations in CD suggest a rather unified picture hinting towards converging oncogenic pathways.},
  language  = {en}
}
@article{HornMitesserHovestadtetal.2019,
  author    = {Horn, Melanie and Mitesser, Oliver and Hovestadt, Thomas and Yoshii, Taishi and Rieger, Dirk and Helfrich-F{\"o}rster, Charlotte},
  title     = {The circadian clock improves fitness in the fruit fly, Drosophila melanogaster},
  series = {Frontiers in Physiology},
  volume    = {10},
  journal   = {Frontiers in Physiology},
  number    = {1374},
  issn      = {1664-042X},
  doi       = {10.3389/fphys.2019.01374},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195738},
  year      = {2019},
  abstract  = {It is assumed that a properly timed circadian clock enhances fitness, but only few studies have truly demonstrated this in animals. We raised each of the three classical Drosophila period mutants for >50 generations in the laboratory in competition with wildtype flies. The populations were either kept under a conventional 24-h day or under cycles that matched the mutant's natural cycle, i.e., a 19-h day in the case of pers mutants and a 29-h day for perl mutants. The arrhythmic per0 mutants were grown together with wildtype flies under constant light that renders wildtype flies similar arrhythmic as the mutants. In addition, the mutants had to compete with wildtype flies for two summers in two consecutive years under outdoor conditions. We found that wildtype flies quickly outcompeted the mutant flies under the 24-h laboratory day and under outdoor conditions, but perl mutants persisted and even outnumbered the wildtype flies under the 29-h day in the laboratory. In contrast, pers and per0 mutants did not win against wildtype flies under the 19-h day and constant light, respectively. Our results demonstrate that wildtype flies have a clear fitness advantage in terms of fertility and offspring survival over the period mutants and - as revealed for perl mutants - this advantage appears maximal when the endogenous period resonates with the period of the environment. However, the experiments indicate that perl and pers persist at low frequencies in the population even under the 24-h day. This may be a consequence of a certain mating preference of wildtype and heterozygous females for mutant males and time differences in activity patterns between wildtype and mutants.},
  language  = {en}
}
@article{FathyFawzyHintzscheetal.2019,
  author    = {Fathy, Moustafa and Fawzy, Michael Atef and Hintzsche, Henning and Nikaido, Toshio and Dandekar, Thomas and Othman, Eman M.},
  title     = {Eugenol exerts apoptotic effect and modulates the sensitivity of HeLa cells to cisplatin and radiation},
  series = {Molecules},
  volume    = {24},
  journal   = {Molecules},
  number    = {21},
  issn      = {1420-3049},
  doi       = {10.3390/molecules24213979},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193227},
  pages     = {3979},
  year      = {2019},
  abstract  = {Eugenol is a phytochemical present in different plant products, e.g., clove oil. Traditionally, it is used against a number of different disorders and it was suggested to have anticancer activity. In this study, the activity of eugenol was evaluated in a human cervical cancer (HeLa) cell line and cell proliferation was examined after treatment with various concentrations of eugenol and different treatment durations. Cytotoxicity was tested using lactate dehydrogenase (LDH) enzyme leakage. In order to assess eugenol's potential to act synergistically with chemotherapy and radiotherapy, cell survival was calculated after eugenol treatment in combination with cisplatin and X-rays. To elucidate its mechanism of action, caspase-3 activity was analyzed and the expression of various genes and proteins was checked by RT-PCR and western blot analyses. Eugenol clearly decreased the proliferation rate and increased LDH release in a concentration- and time-dependent manner. It showed synergistic effects with cisplatin and X-rays. Eugenol increased caspase-3 activity and the expression of Bax, cytochrome c (Cyt-c), caspase-3, and caspase-9 and decreased the expression of B-cell lymphoma (Bcl)-2, cyclooxygenase-2 (Cox-2), and interleukin-1 beta (IL-1β) indicating that eugenol mainly induced cell death by apoptosis. In conclusion, eugenol showed antiproliferative and cytotoxic effects via apoptosis and also synergism with cisplatin and ionizing radiation in the human cervical cancer cell line.},
  language  = {en}
}
@article{MateosKangKloppetal.2019,
  author    = {Mateos, Mariana and Kang, Du and Klopp, Christophe and Parrinello, Hugues and Garc{\´i}a-Olaz{\´a}bal, Mateo and Schumer, Molly and Jue, Nathaniel K. and Guiguen, Yann and Schartl, Manfred},
  title     = {Draft genome assembly and annotation of the Gila Topminnow Poeciliopsis occidentalis},
  series = {Frontiers in Ecology and Evolution},
  volume    = {7},
  journal   = {Frontiers in Ecology and Evolution},
  number    = {404},
  issn      = {2296-701X},
  doi       = {10.3389/fevo.2019.00404},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-190339},
  year      = {2019},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{KunzGoetzSaueretal.2019,
  author    = {Kunz, Tobias C. and G{\"o}tz, Ralph and Sauer, Markus and Rudel, Thomas},
  title     = {Detection of chlamydia developmental forms and secreted effectors by expansion microscopy},
  series = {Frontiers in Cellular and Infection Microbiology},
  volume    = {9},
  journal   = {Frontiers in Cellular and Infection Microbiology},
  number    = {276},
  issn      = {2235-2988},
  doi       = {10.3389/fcimb.2019.00276},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195716},
  year      = {2019},
  abstract  = {Expansion microscopy (ExM) is a novel tool to improve the resolution of fluorescence-based microscopy that has not yet been used to visualize intracellular pathogens. Here we show the expansion of the intracellular pathogen Chlamydia trachomatis, enabling to differentiate its two distinct forms, catabolic active reticulate bodies (RB) and infectious elementary bodies (EB), on a conventional confocal microscope. We show that ExM enables the possibility to precisely locate chlamydial effector proteins, such as CPAF or Cdu1, within and outside of the chlamydial inclusion. Thus, we claim that ExM offers the possibility to address a broad range of questions and may be useful for further research on various intracellular pathogens.},
  language  = {en}
}
@article{HeydarianYangSchweinlinetal.2019,
  author    = {Heydarian, Motaharehsadat and Yang, Tao and Schweinlin, Matthias and Steinke, Maria and Walles, Heike and Rudel, Thomas and Kozjak-Pavlovic, Vera},
  title     = {Biomimetic human tissue model for long-term study of Neisseria gonorrhoeae infection},
  series = {Frontiers in Microbiology},
  volume    = {10},
  journal   = {Frontiers in Microbiology},
  number    = {1740},
  issn      = {1664-302X},
  doi       = {10.3389/fmicb.2019.01740},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197912},
  year      = {2019},
  abstract  = {Gonorrhea is the second most common sexually transmitted infection in the world and is caused by Gram-negative diplococcus Neisseria gonorrhoeae. Since N. gonorrhoeae is a human-specific pathogen, animal infection models are only of limited use. Therefore, a suitable in vitro cell culture model for studying the complete infection including adhesion, transmigration and transport to deeper tissue layers is required. In the present study, we generated three independent 3D tissue models based on porcine small intestinal submucosa (SIS) scaffold by co-culturing human dermal fibroblasts with human colorectal carcinoma, endometrial epithelial, and male uroepithelial cells. Functional analyses such as transepithelial electrical resistance (TEER) and FITC-dextran assay indicated the high barrier integrity of the created monolayer. The histological, immunohistochemical, and ultra-structural analyses showed that the 3D SIS scaffold-based models closely mimic the main characteristics of the site of gonococcal infection in human host including the epithelial monolayer, the underlying connective tissue, mucus production, tight junction, and microvilli formation. We infected the established 3D tissue models with different N. gonorrhoeae strains and derivatives presenting various phenotypes regarding adhesion and invasion. The results indicated that the disruption of tight junctions and increase in interleukin production in response to the infection is strain and cell type-dependent. In addition, the models supported bacterial survival and proved to be better suitable for studying infection over the course of several days in comparison to commonly used Transwell® models. This was primarily due to increased resilience of the SIS scaffold models to infection in terms of changes in permeability, cell destruction and bacterial transmigration. In summary, the SIS scaffold-based 3D tissue models of human mucosal tissues represent promising tools for investigating N. gonorrhoeae infections under close-to-natural conditions.},
  language  = {en}
}
@phdthesis{Neubert2019,
  author    = {Neubert, Franziska},
  title     = {Markierung postsynaptischer Proteine f{\"u}r die hochaufl{\"o}sende Fluoreszenzmikroskopie},
  doi       = {10.25972/OPUS-19239},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-192394},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Das menschliche Gehirn ist ein Organ, das aufgrund seiner Komplexit{\"a}t und zellul{\"a}ren Diversit{\"a}t noch am wenigsten verstanden ist. Eine der Ursachen daf{\"u}r sind zahlreiche Herausforderungen in diversen neurobiologischen Bild-gebungsverfahren. Erst seit der Erfindung der hochaufl{\"o}senden Fluoreszenz-mikroskopie ist es m{\"o}glich, Strukturen unterhalb der Beugungsgrenze zu visua-lisieren und somit eine maximale Aufl{\"o}sung von bis zu 20 nm zu erreichen. Zus{\"a}tzlich h{\"a}ngt die F{\"a}higkeit, biologische Strukturen aufzul{\"o}sen, von der Markierungs-gr{\"o}ße und -dichte ab. Derzeit ist die h{\"a}ufigste Methode zur Proteinf{\"a}rbung die indirekte Antik{\"o}rperf{\"a}rbung, bei der ein Fluorophor-markierter Sekund{\"a}rantik{\"o}rper an einen Epitop-spezifischen Prim{\"a}rantik{\"o}rper bindet. Dabei kann der Abstand von Zielstruktur und Fluorophor bis zu 30 nm betragen, was eine Aufl{\"o}sungs-verminderung zur Folge haben kann. Aufgrund dessen wurden in dieser Arbeit alternative Markierungsmethoden getestet, um postsynaptische Proteine sicht-bar zu machen. Zun{\"a}chst wurde der postsynaptische N-Methyl-D-Aspartat (NMDA)-Rezeptor mit Hilfe konventioneller indirekter Antik{\"o}rperf{\"a}rbung markiert. Hier war die NR1-Untereinheit des NMDA-Rezeptors von besonderem Interesse, da diese in der Autoimmunerkrankung Anti-NMDA-Rezeptor-Enzephalitis invol-viert ist. Patienten dieser seltenen Krankheit bilden Autoantik{\"o}rper gegen die NR1-Untereinheit, wodurch ein schneller reversibler Verlust der NMDA-Rezeptoren auf der Postsynapse induziert wird. Wichtige Informationen k{\"o}nnen nicht mehr ausreichend weitergegeben werden, was psychiatrische und neurologi-sche St{\"o}rungen zur Folge hat. In dieser Arbeit wurden sowohl kommerzielle NR1-Antik{\"o}rper, als auch rekombinante monoklonale NR1-Antik{\"o}rper von Patien-ten mit Anti-NMDA-Rezeptor-Enzephalitis getestet. In konfokalen und in hochaufgel{\"o}sten SIM- (engl. structured illumination microscopy) und dSTORM- (engl. direct stochastic optical reconstruction microscopy) Messun-gen konnten kommerzielle NR1-Antik{\"o}rper keine erfolgreichen F{\"a}rbungen erzielen. Dagegen erwiesen sich die rekombinanten monoklonalen NR1-Patientenantik{\"o}rper als sehr spezifisch, sowohl in prim{\"a}ren Neuronen als auch im Hippocampus von murinen Gehirnschnitten und lieferten gute Kolokalisati-onen mit dem postsynaptischen Markerprotein Homer. Um die optische Aufl{\"o}sung zu verbessern, wurde eine neue Markierungs-methode mit sog. „Super-Binde-Peptiden" (SBPs) getestet. SBPs sind modifi-zierte Peptide, die erh{\"o}hte Affinit{\"a}ten und Spezifit{\"a}ten aufweisen und mit ei-ner Gr{\"o}ße von ~ 2,5 nm wesentlich kleiner als Antik{\"o}rper sind. In dieser Arbeit best{\"a}tigte sich ein kleines hochspezifisches SPB, das an den Fluoreszenzfarb-stoff Tetra- methylrhodamin (TMR) gekoppelt ist, als effektiver Marker f{\"u}r das Ankerpro-tein Gephyrin. Gephyrin ist f{\"u}r die Lokalisation und Verankerung einiger post-synaptischer Rezeptoren zust{\"a}ndig, indem es sie mit dem Cytoskelett der Zelle verbindet. SIM-Messungen in prim{\"a}ren Neuronen zeigten eine bessere Clus-terrepr{\"a}sentation bei der F{\"a}rbung von Gephyrin mit SBPs, als mit Antik{\"o}rper-f{\"a}rbung. Zus{\"a}tzlich wurden Kolokalisationsanalysen von Gephyrin zusammen mit dem inhibito-rischen pr{\"a}synaptischen vesikul{\"a}ren GABA-Transporter VGAT durchgef{\"u}hrt. Eine weitere F{\"a}rbemethode stellte die bioorthogonale Click-F{\"a}rbung durch die Erweiterung des eukaryotischen genetischen Codes (engl. genetic code ex-pansion, GCE) dar. Dabei wurde eine unnat{\"u}rliche, nicht-kanonische Amino-s{\"a}ure (engl. non-canonical amino acid, ncAA) ins Zielprotein eingebaut und in Kombination mit der Click-Chemie ortsspezifisch mit organischen Tetrazin-Farbstoff-Konjugaten angef{\"a}rbt. Organische Fluorophore haben den Vorteil, dass sie mit einer Gr{\"o}ße von 0,5 - 2 nm sehr klein sind und damit die nat{\"u}rli-chen Funktionen der Proteine in der Zelle kaum beeinflussen. In dieser Arbeit wurde zum ersten Mal gezeigt, dass der tetramere postsynaptische NMDA-Rezeptor durch die Amber-Supres-sionsmethode bioorthogonal angef{\"a}rbt werden konnte. Aus sieben verschiede-nen Amber-Mutanten der NR1-Untereinheit stellte sich die Y392TAG-NR1-Mutante als diejenige mit der besten Proteinexpression, F{\"a}rbeeffizienz und rezeptorfunktionalit{\"a}t heraus. Dies konnte durch Fluoreszenzmikroskopie- und Whole-Cell Patch-Clamp-Experimenten gezeigt werden. Die bioorthogo-nale Click-F{\"a}rbung durch GCE eignete sich f{\"u}r die F{\"a}rbung des NMDA-Rezeptors in verschiedenen Zelllinien, mit unterschiedlichen Tetrazin-Farbstoff-Konjugaten und f{\"u}r Lebendzellexperimente. In dSTORM-Messungen erwies sich das Tetrazin-Cy5-Farbstoff-Konjugat als ideal aufgrund seiner Gr{\"o}-ße, Photostabilit{\"a}t, Helligkeit und seines geeigneten Blinkverhaltens, sodass eine homogene NMDA-Rezeptorverteilung auf der Zellmembran gezeigt wer-den konnte. NR1-Antik{\"o}rperf{\"a}rbungen wiesen dagegen starke Clusterbildun-gen auf. Die Ergebnisse konnten belegen, dass kleinere Farbstoffe eine deut-lich bessere Zug{\"a}nglichkeit zu ihrem Zielprotein haben und somit besser f{\"u}r die hochaufl{\"o}sende Fluoreszenzmikroskopie geeignet sind.},
  subject      = {hochaufl{\"o}sende Fluoreszenzmikroskopie},
  language  = {de}
}
@phdthesis{Griffoni2019,
  author    = {Griffoni, Chiara},
  title     = {Towards advanced immunocompetent skin wound models for in vitro drug evaluation},
  doi       = {10.25972/OPUS-19212},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-192125},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Current preclinical models used to evaluate novel therapies for improved healing include both in vitro and in vivo methods. However, ethical concerns related to the use of animals as well as the poor physiological translation between animal and human skin wound healing designate in vitro models as a highly relevant and promising platforms for healing investigation. While current in vitro 3D skin models recapitulate a mature tissue with healing properties, they still represent a simplification of the in vivo conditions, where for example the inflammatory response originating after wound formation involves the contribution of immune cells. Macrophages are among the main contributors to the inflammatory response and regulate its course thanks to their plasticity. Therefore, their implementation into in vitro skin could greatly increase the physiological relevance of the models. As no full-thickness immunocompetent skin model containing macrophages has been reported so far, the parameters necessary for a successful triple co-culture of fibroblasts, keratinocytes and macrophages were here investigated. At first, cell source and culture timed but also an implementation strategy for macrophages were deter-mined. The implementation of macrophages into the skin model focused on the minimization of the culture time to preserve immune cell viability and phenotype, as the environment has a major influence on cell polarization and cytokine production. To this end, incorporation of macrophages in 3D gels prior to the combination with skin models was selected to better mimic the in vivo environment. Em-bedded in collagen hydrogels, macrophages displayed a homogeneous cell distribution within the gel, preserving cell viability, their ability to respond to stimuli and their capability to migrate through the matrix, which are all needed during the involvement of macrophages in the inflammatory response. Once established how to introduce macrophages into skin models, different culture media were evaluated for their effects on primary fibroblasts, keratinocytes and macrophages, to identify a suitable medium composition for the culture of immunocompetent skin. The present work confirmed that each cell type requires a different supplement combination for maintaining functional features and showed for the first time that media that promote and maintain a mature skin structure have negative effects on primary macrophages. Skin differentiation media negatively affected macrophages in terms of viability, morphology, ability to respond to pro- and anti-inflammatory stimuli and to migrate through a collagen gel. The combination of wounded skin equivalents and macrophage-containing gels con-firmed that culture medium inhibits macrophage participation in the inflammatory response that oc-curs after wounding. The described macrophage inclusion method for immunocompetent skin creation is a promising approach for generating more relevant skin models. Further optimization of the co-cul-ture medium will potentially allow mimicking a physiological inflammatory response, enabling to eval-uate the effects novel drugs designed for improved healing on improved in vitro models.},
  subject      = {Haut},
  language  = {en}
}