From Single Cells to Engineered and Explanted Tissues

Bergmann, Simone; Steinert, Michael

doi:10.1016/bs.ircmb.2015.06.003

Cited by 15 publications

(10 citation statements)

References 213 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5, 10 Indeed, it is widely recognized there is an urgent need for advanced in vitro cell culture models that mimic the complex 3-D architecture, multicellular complexity and phenotypic characteristics of in vivo tissues for use in predictive human disease modeling, including infectious disease. 4, 5, 11–13 Accordingly, achieving a deeper understanding of host–pathogen interactions at the intestinal mucosa requires cell culture models that incorporate 3-D architecture, differentiation and multicellular complexity to characterize the interaction between epithelial cells and macrophages during enteric infection.…”

Section: Introductionmentioning

confidence: 99%

Three-dimensional organotypic co-culture model of intestinal epithelial cells and macrophages to study Salmonella enterica colonization patterns

et al. 2017

View full text Add to dashboard Cite

Three-dimensional models of human intestinal epithelium mimic the differentiated form and function of parental tissues often not exhibited by two-dimensional monolayers and respond to Salmonella in key ways that reflect in vivo infections. To further enhance the physiological relevance of three-dimensional models to more closely approximate in vivo intestinal microenvironments encountered by Salmonella, we developed and validated a novel three-dimensional co-culture infection model of colonic epithelial cells and macrophages using the NASA Rotating Wall Vessel bioreactor. First, U937 cells were activated upon collagen-coated scaffolds. HT-29 epithelial cells were then added and the three-dimensional model was cultured in the bioreactor until optimal differentiation was reached, as assessed by immunohistochemical profiling and bead uptake assays. The new co-culture model exhibited in vivo-like structural and phenotypic characteristics, including three-dimensional architecture, apical-basolateral polarity, well-formed tight/adherens junctions, mucin, multiple epithelial cell types, and functional macrophages. Phagocytic activity of macrophages was confirmed by uptake of inert, bacteria-sized beads. Contribution of macrophages to infection was assessed by colonization studies of Salmonella pathovars with different host adaptations and disease phenotypes (Typhimurium ST19 strain SL1344 and ST313 strain D23580; Typhi Ty2). In addition, Salmonella were cultured aerobically or microaerobically, recapitulating environments encountered prior to and during intestinal infection, respectively. All Salmonella strains exhibited decreased colonization in co-culture (HT-29-U937) relative to epithelial (HT-29) models, indicating antimicrobial function of macrophages. Interestingly, D23580 exhibited enhanced replication/survival in both models following invasion. Pathovar-specific differences in colonization and intracellular co-localization patterns were observed. These findings emphasize the power of incorporating a series of related three-dimensional models within a study to identify microenvironmental factors important for regulating infection.

show abstract

Section: Introductionmentioning

confidence: 99%

Three-dimensional organotypic co-culture model of intestinal epithelial cells and macrophages to study Salmonella enterica colonization patterns

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The term organoid ("organ-like") has been used to describe a variety of 3-D models that resemble in vivo tissues. Historically, this included models engineered with different technologies using cell lines, stem cells, primary cells, or tissue explants either embedded in or cultured on top of ECM scaffolds that allow cells to self-assemble into 3-D structures (8,12,143,145,146,169,171,(221)(222)(223)(224)(225)(226)(227)(228)(229). Advances in stem cell biology led to a recent terminology shift to more specifically define organoids as 3-D models derived from stem cells, progenitor cells, or primary explants (222,(230)(231)(232)(233)(234)(235)(236)(237)(238).…”

Section: Modeling the Microenvironment: 3-d Models For Infectious Dismentioning

confidence: 99%

Modeling Host-Pathogen Interactions in the Context of the Microenvironment: Three-Dimensional Cell Culture Comes of Age

et al. 2018

View full text Add to dashboard Cite

Tissues and organs provide the structural and biochemical landscapes upon which microbial pathogens and commensals function to regulate health and disease. While flat two-dimensional (2-D) monolayers composed of a single cell type have provided important insight into understanding host-pathogen interactions and infectious disease mechanisms, these reductionist models lack many essential features present in the native host microenvironment that are known to regulate infection, including three-dimensional (3-D) architecture, multicellular complexity, commensal microbiota, gas exchange and nutrient gradients, and physiologically relevant biomechanical forces (e.g., fluid shear, stretch, compression). A major challenge in tissue engineering for infectious disease research is recreating this dynamic 3-D microenvironment (biological, chemical, and physical/mechanical) to more accurately model the initiation and progression of host-pathogen interactions in the laboratory. Here we review selected 3-D models of human intestinal mucosa, which represent a major portal of entry for infectious pathogens and an important niche for commensal microbiota. We highlight seminal studies that have used these models to interrogate host-pathogen interactions and infectious disease mechanisms, and we present this literature in the appropriate historical context. Models discussed include 3-D organotypic cultures engineered in the rotating wall vessel (RWV) bioreactor, extracellular matrix (ECM)-embedded/organoid models, and organ-on-a-chip (OAC) models. Collectively, these technologies provide a more physiologically relevant and predictive framework for investigating infectious disease mechanisms and antimicrobial therapies at the intersection of the host, microbe, and their local microenvironments.

show abstract

“…A number of studies indicated that L. pneumophila is highly adapted and manages to infect a wide range of protozoan and metazoan hosts (Hilbi et al, 2011 ; Bergmann and Steinert, 2015 ; Hsu et al, 2015 ). This suggests that many protozoan host species and other interaction partners of L. pneumophila in the environment remain to be discovered.…”

Section: Protozoa As Environmental Niches Of Legionella mentioning

confidence: 99%

“…The distinct features of the protozoan genera Acanthamoeba and Dictyostelium have been particularly useful in examining the ecology and cellular host-interactions of L. pneumophila . Given the similarity of the infection process in amoebae and macrophages, the amoebae are powerful models to study bacteria-macrophage interactions (Hilbi et al, 2007 ; Escoll et al, 2013 ; Hoffmann et al, 2013 ; Bergmann and Steinert, 2015 ). Acanthamoeba has often been found in Legionella -positive habitats and has an extremely wide distribution.…”

Section: Acanthamoeba As a Natural And Model Host Of mentioning

confidence: 99%

Acanthamoeba and Dictyostelium as Cellular Models for Legionella Infection

Swart

Harrison

Eichinger

et al. 2018

Front. Cell. Infect. Microbiol.

Self Cite

View full text Add to dashboard Cite

Environmental bacteria of the genus Legionella naturally parasitize free-living amoebae. Upon inhalation of bacteria-laden aerosols, the opportunistic pathogens grow intracellularly in alveolar macrophages and can cause a life-threatening pneumonia termed Legionnaires' disease. Intracellular replication in amoebae and macrophages takes place in a unique membrane-bound compartment, the Legionella-containing vacuole (LCV). LCV formation requires the bacterial Icm/Dot type IV secretion system, which translocates literally hundreds of “effector” proteins into host cells, where they modulate crucial cellular processes for the pathogen's benefit. The mechanism of LCV formation appears to be evolutionarily conserved, and therefore, amoebae are not only ecologically significant niches for Legionella spp., but also useful cellular models for eukaryotic phagocytes. In particular, Acanthamoeba castellanii and Dictyostelium discoideum emerged over the last years as versatile and powerful models. Using genetic, biochemical and cell biological approaches, molecular interactions between amoebae and Legionella pneumophila have recently been investigated in detail with a focus on the role of phosphoinositide lipids, small and large GTPases, autophagy components and the retromer complex, as well as on bacterial effectors targeting these host factors.

show abstract

From Single Cells to Engineered and Explanted Tissues

Cited by 15 publications

References 213 publications

Three-dimensional organotypic co-culture model of intestinal epithelial cells and macrophages to study Salmonella enterica colonization patterns

Three-dimensional organotypic co-culture model of intestinal epithelial cells and macrophages to study Salmonella enterica colonization patterns

Modeling Host-Pathogen Interactions in the Context of the Microenvironment: Three-Dimensional Cell Culture Comes of Age

Acanthamoeba and Dictyostelium as Cellular Models for Legionella Infection

Contact Info

Product

Resources

About