scholarly journals Novel three-dimensional biochip pulmonary sarcoidosis model

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0245805
Author(s):  
Tess M. Calcagno ◽  
Chongxu Zhang ◽  
Runxia Tian ◽  
Babak Ebrahimi ◽  
Mehdi Mirsaeidi
Keyword(s):  
Current Model ◽  
Three Dimensional ◽  
Granulomatous Inflammation ◽  
Pulmonary Sarcoidosis ◽  
Membrane Model ◽  
Gm Csf ◽  
Elisa Testing ◽  
On Chip ◽  
System Disorder

Sarcoidosis is a multi-system disorder of granulomatous inflammation which most commonly affects the lungs. Its etiology and pathogenesis are not well defined in part due to the lack of reliable modeling. Here, we present the development of an in vitro three-dimensional lung-on-chip biochip designed to mimic granuloma formation. A lung on chip fluidic macrodevice was developed and added to our previously developed a lung-on-membrane model (LOMM). Granulomas were cultured from blood samples of patients with sarcoidosis and then inserted in the air-lung-interface of the microchip to create a three-dimensional biochip pulmonary sarcoidosis model (3D BSGM). Cytokines were measured after 48 hours. ELISA testing was performed to measure cytokine response difference between LOMM with 3D BSGM. There were statistically significant differences in IL-1ß (P = 0.001953), IL-6 (P = 0.001953), GM-CSF (P = 0.001953), and INF-γ expressions (P = 0.09375) between two groups. The current model represents the first 3D biochip sarcoidosis model created by adding a microfluidics system to a dual-chambered lung on membrane model and introducing developed sarcoid-granuloma to its air-lung-interface.

scholarly journals Novel Three-Dimensional Organoid Sarcoidosis Granuloma Model

2020 ◽  
Author(s):  
Tess M. Calcagno ◽  
Chongxu Zhang ◽  
Runxia Tian ◽  
Babak Ebrahimi ◽  
Mehdi Mirsaeidi
Keyword(s):  
Current Model ◽  
Three Dimensional ◽  
Granulomatous Inflammation ◽  
Lung Model ◽  
Membrane Model ◽  
Gm Csf ◽  
Sarcoid Granuloma ◽  
On Chip ◽  
System Disorder

AbstractSarcoidosis is a multi-system disorder of granulomatous inflammation which most commonly affects the lungs. Its etiology and pathogenesis are not well defined in part due to the lack of reliable modeling. This article presents the development of a novel in vitro three-dimensional lung-on-chip organoid designed to mimic granuloma formation. A lung on chip fluidic macrodevice with three channels for cell culture insertion was developed and added to the previously developed a lung-on-membrane model. Granulomas were cultured from blood samples of patients with sarcoidosis and then inserted in the air-lung-interface (ALI) of the microchip to create a three-dimensional organoid sarcoidosis model (OSGM). The model was tested for cell viability with fibroblasts. We measured the cytokine profiles in medium of OSGM and compared with lung model without granuloma. Concentration of IL-1beta, Il-6, GM-CSF, and IFN-gamma were found significantly higher in OSGM group. The current model represents the first 3D OSGM created by adding a microfluidics system to a dual-chambered lung on membrane model and introducing developed sarcoid-granuloma to its ALI.

scholarly journals Engineered Heterochronic Parabiosis in 3D Microphysiological System for Identification of Muscle Rejuvenating Factors

2020 ◽  
Author(s):  
Yunki Lee ◽  
Jeongmoon J. Choi ◽  
Song Ih Ahn ◽  
Nan Hee Leea ◽  
Woojin M. Han ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Function ◽  
Three Dimensional ◽  
Muscle Stem Cell ◽  
Organ Systems ◽  
Systemic Factors ◽  
Underlying Mechanisms ◽  
On Chip

AbstractExposure of aged mice to a young systemic milieu revealed remarkable rejuvenation effects on aged tissues, including skeletal muscle. Although some candidate factors have been identified, the exact identity and the underlying mechanisms of putative rejuvenating factors remain elusive, mainly due to the complexity of in vivo parabiosis. Here, we present an in vitro muscle parabiosis system that integrates young- and old-muscle stem cell vascular niche on a three-dimensional microfluidic platform designed to recapitulate key features of native muscle stem cell microenvironment. This innovative system enables mechanistic studies of cellular dynamics and molecular interactions within the muscle stem cell niche, especially in response to conditional extrinsic stimuli of local and systemic factors. We demonstrate that vascular endothelial growth factor (VEGF) signaling from endothelial cells and myotubes synergistically contribute to the rejuvenation of the aged muscle stem cell function. Moreover, with the adjustable on-chip system, we can mimic both blood transfusion and parabiosis and detect the time-varying effects of anti-geronic and pro-geronic factors in a single organ or multi-organ systems. Our unique approach presents a complementary in vitro model to supplement in vivo parabiosis for identifying potential anti-geronic factors responsible for revitalizing aging organs.

scholarly journals Digital Twins for Tissue Culture Techniques—Concepts, Expectations, and State of the Art

Processes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 447
Author(s):  
Johannes Möller ◽  
Ralf Pörtner
Keyword(s):  
Tissue Culture ◽  
Mathematical Models ◽  
Product Life Cycle ◽  
State Of The Art ◽  
Three Dimensional ◽  
Culture Techniques ◽  
Digital Twins ◽  
On Chip ◽  
Tissue Culture Techniques

Techniques to provide in vitro tissue culture have undergone significant changes during the last decades, and current applications involve interactions of cells and organoids, three-dimensional cell co-cultures, and organ/body-on-chip tools. Efficient computer-aided and mathematical model-based methods are required for efficient and knowledge-driven characterization, optimization, and routine manufacturing of tissue culture systems. As an alternative to purely experimental-driven research, the usage of comprehensive mathematical models as a virtual in silico representation of the tissue culture, namely a digital twin, can be advantageous. Digital twins include the mechanistic of the biological system in the form of diverse mathematical models, which describe the interaction between tissue culture techniques and cell growth, metabolism, and the quality of the tissue. In this review, current concepts, expectations, and the state of the art of digital twins for tissue culture concepts will be highlighted. In general, DT’s can be applied along the full process chain and along the product life cycle. Due to the complexity, the focus of this review will be especially on the design, characterization, and operation of the tissue culture techniques.

scholarly journals Single-cell transcriptomics elucidates in vitro reprogramming of human intestinal epithelium cultured in a physiodynamic gut-on-a-chip

2021 ◽  
Author(s):  
Woojung Shin ◽  
Zhe Su ◽  
S. Stephen Yi ◽  
Hyun Jung Kim
Keyword(s):  
Single Cell ◽  
Intestinal Epithelium ◽  
Drug Transport ◽  
Three Dimensional ◽  
Cancer Cell Line ◽  
Static Condition ◽  
On Chip ◽  
Epithelial Layers

The microphysiological human gut-on-a-chip has demonstrated in vivo-relevant cellular fidelity of intestinal epithelium compared to its cultures in a static condition. Microfluidic control of morphogen gradients and mechanical cues robustly induced morphological histogenesis with villi-like three-dimensional (3D) microarchitecture, lineage-associated cytodifferentiation, and physiological functions of a human intestinal Caco-2 epithelium. However, transcriptomic dynamics that orchestrates morphological and functional reprogramming of the epithelium in a microphysiological culture remains elusive. Single-cell transcriptomic analysis revealed that a gut-on-a-chip culture that offers physiological motions and flow drives three distinctive subclusters that offer distinct gene expression and unique spatial representation in 3D epithelial layers. The pseudotemporal trajectory of individual cells visualized the evolutionary transition from ancestral genotypes in static cultures into more heterogeneous phenotypes in physiodynamic cultures on cell cycles, differentiation, and intestinal functions including digestion, absorption, drug transport, and metabolism of xenobiotics. Furthermore, the inversed transcriptomic signature of oncogenes and tumor-suppressor genes of Caco-2 cells verified that a gut-on-a-chip culture drives a postmitotic reprogramming of cancer-associated phenotypes. Thus, we discovered that a physiodynamic on-chip culture is necessary and sufficient for a cancer cell line to be reprogrammed to elicit in vivo-relevant heterogeneous cell populations with restored normal physiological signatures.

scholarly journals Human Adipose Derived Cells in Two- and Three-Dimensional Cultures: Functional Validation of an In Vitro Fat Construct

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Robert Bender ◽  
Michelle McCarthy ◽  
Theodore Brown ◽  
Joanna Bukowska ◽  
Stanley Smith ◽  
...  
Keyword(s):  
Adipogenic Differentiation ◽  
Three Dimensional ◽  
3D Culture ◽  
Stromal Vascular Fraction ◽  
The United States ◽  
Nonalcoholic Fatty Liver ◽  
3 Dimensional ◽  
Treatment Of Obesity ◽  
On Chip

Obesity, defined as a body mass index of 30 kg/m2 or above, has increased considerably in incidence and frequency within the United States and globally. Associated comorbidities including cardiovascular disease, type 2 diabetes mellitus, metabolic syndrome, and nonalcoholic fatty liver disease have led to a focus on the mechanisms promoting the prevention and treatment of obesity. Commonly utilized in vitro models employ human or mouse preadipocyte cell lines in a 2-dimensional (2D) format. Due to the structural, biochemical, and biological limitations of these models, increased attention has been placed on “organ on a chip” technologies for a 3-dimensional (3D) culture. Herein, we describe a method employing cryopreserved primary human stromal vascular fraction (SVF) cells and a human blood product-derived biological scaffold to create a 3D adipose depot in vitro. The “fat-on-chip” 3D cultures have been validated relative to 2D cultures based on proliferation, flow cytometry, adipogenic differentiation, confocal microscopy/immunofluorescence, and functional assays (adipokine secretion, glucose uptake, and lipolysis). Thus, the in vitro culture system demonstrates the critical characteristics required for a humanized 3D white adipose tissue (WAT) model.

scholarly journals Compliant 3D frameworks instrumented with strain sensors for characterization of millimeter-scale engineered muscle tissues

2021 ◽  
Vol 118 (19) ◽  
pp. e2100077118
Author(s):  
Hangbo Zhao ◽  
Yongdeok Kim ◽  
Heling Wang ◽  
Xin Ning ◽  
Chenkai Xu ◽  
...  
Keyword(s):  
Disease Modeling ◽  
Three Dimensional ◽  
High Sensitivity ◽  
Strain Sensors ◽  
High Temporal Resolution ◽  
On Chip ◽  
Contractile Forces ◽  
Traditional Approaches ◽  
And Control

Tissue-on-chip systems represent promising platforms for monitoring and controlling tissue functions in vitro for various purposes in biomedical research. The two-dimensional (2D) layouts of these constructs constrain the types of interactions that can be studied and limit their relevance to three-dimensional (3D) tissues. The development of 3D electronic scaffolds and microphysiological devices with geometries and functions tailored to realistic 3D tissues has the potential to create important possibilities in advanced sensing and control. This study presents classes of compliant 3D frameworks that incorporate microscale strain sensors for high-sensitivity measurements of contractile forces of engineered optogenetic muscle tissue rings, supported by quantitative simulations. Compared with traditional approaches based on optical microscopy, these 3D mechanical frameworks and sensing systems can measure not only motions but also contractile forces with high accuracy and high temporal resolution. Results of active tension force measurements of engineered muscle rings under different stimulation conditions in long-term monitoring settings for over 5 wk and in response to various chemical and drug doses demonstrate the utility of such platforms in sensing and modulation of muscle and other tissues. Possibilities for applications range from drug screening and disease modeling to biohybrid robotic engineering.

scholarly journals Application of lung microphysiological systems to COVID-19 modeling and drug discovery: a review

2021 ◽  
Author(s):  
Argus M. Sun ◽  
Tyler Hoffman ◽  
Bao Q. Luu ◽  
Nureddin Ashammakhi ◽  
Song Li
Keyword(s):  
Drug Development ◽  
High Throughput Screening ◽  
Current Model ◽  
3D Structure ◽  
Three Dimensional ◽  
Cell Types ◽  
Model Systems ◽  
Biological Interactions ◽  
Microphysiological Systems

AbstractThere is a pressing need for effective therapeutics for coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The process of drug development is a costly and meticulously paced process, where progress is often hindered by the failure of initially promising leads. To aid this challenge, in vitro human microphysiological systems need to be refined and adapted for mechanistic studies and drug screening, thereby saving valuable time and resources during a pandemic crisis. The SARS-CoV-2 virus attacks the lung, an organ where the unique three-dimensional (3D) structure of its functional units is critical for proper respiratory function. The in vitro lung models essentially recapitulate the distinct tissue structure and the dynamic mechanical and biological interactions between different cell types. Current model systems include Transwell, organoid and organ-on-a-chip or microphysiological systems (MPSs). We review models that have direct relevance toward modeling the pathology of COVID-19, including the processes of inflammation, edema, coagulation, as well as lung immune function. We also consider the practical issues that may influence the design and fabrication of MPS. The role of lung MPS is addressed in the context of multi-organ models, and it is discussed how high-throughput screening and artificial intelligence can be integrated with lung MPS to accelerate drug development for COVID-19 and other infectious diseases.

scholarly journals Engineered 3D Polymer and Hydrogel Microenvironments for Cell Culture Applications

2019 ◽  
Vol 6 (4) ◽  
pp. 113 ◽  
Author(s):  
Daniel Fan ◽  
Urs Staufer ◽  
Angelo Accardo
Keyword(s):  
Cell Biology ◽  
Three Dimensional ◽  
Research Areas ◽  
Current Review ◽  
Trade Offs ◽  
In Vitro Drug Screening ◽  
Manufacturing Techniques ◽  
On Chip ◽  
Printing Techniques

The realization of biomimetic microenvironments for cell biology applications such as organ-on-chip, in vitro drug screening, and tissue engineering is one of the most fascinating research areas in the field of bioengineering. The continuous evolution of additive manufacturing techniques provides the tools to engineer these architectures at different scales. Moreover, it is now possible to tailor their biomechanical and topological properties while taking inspiration from the characteristics of the extracellular matrix, the three-dimensional scaffold in which cells proliferate, migrate, and differentiate. In such context, there is therefore a continuous quest for synthetic and nature-derived composite materials that must hold biocompatible, biodegradable, bioactive features and also be compatible with the envisioned fabrication strategy. The structure of the current review is intended to provide to both micro-engineers and cell biologists a comparative overview of the characteristics, advantages, and drawbacks of the major 3D printing techniques, the most promising biomaterials candidates, and the trade-offs that must be considered in order to replicate the properties of natural microenvironments.

scholarly journals Presence of Antibodies Binding to Negative Elongation Factor E in Sarcoidosis

2020 ◽  
Vol 9 (3) ◽  
pp. 715 ◽  
Author(s):  
Niklas Baerlecken ◽  
Nils Pursche ◽  
Torsten Witte ◽  
Katja Kniesch ◽  
Marius Höpfner ◽  
...  
Keyword(s):  
Elongation Factor ◽  
Granulomatous Inflammation ◽  
Pulmonary Sarcoidosis ◽  
Protein Array ◽  
Antibody Detection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Derivation Cohort ◽  
Array Technology ◽  
Elisa Testing ◽  
Negative Elongation Factor

Sarcoidosis is characterized by multiorgan involvement and granulomatous inflammation. Its origin is unknown and the potential role of autoimmunity has not been sufficiently determined. We investigated the presence of autoantibodies in sarcoidosis using protein array technology. The derivation cohort consisted of patients with sarcoidosis (n = 25) and controls including autoimmune disease and blood donors (n = 246). In addition, we tested a validation cohort including pulmonary sarcoidosis patients (n = 58) and healthy controls (n = 13). Initially, sera of three patients with sarcoidosis were screened using a protein array with 28.000 proteins against controls. Thereby we identified the Negative Elongation Factor E (NELF-E) as an autoantigen. With confirmatory Enzyme-linked Immunosorbent Assay (ELISA)testing, 29/82 patients (35%) with sarcoidosis had antibodies against NELF-E of the Immunoglobulin (Ig) G type, whereas 18/253 (7%) sera of the controls were positive for NELF-E. Clinically, there was an association of the frequency of NELF-E antibody detection with lung parenchymal involvement and corresponding x-ray types. NELF-E autoantibodies are associated with sarcoidosis and should be further investigated.

scholarly journals Bioengineering a Miniaturized In Vitro 3D Myotube Contraction Monitoring Chip For Modelization of Muscular Dystrophies

2021 ◽  
Author(s):  
Nicolas Rose ◽  
Surabhi Sonam ◽  
Thao Nguyen ◽  
Gianluca Grenci ◽  
Anne Bigot ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Congenital Muscular Dystrophy ◽  
Muscular Disorders ◽  
Adsorption Technology ◽  
Therapeutic Procedures ◽  
On Chip ◽  
Physical And Chemical ◽  
The Impact

Quantification of skeletal muscle functional strength is essential to assess the outcomes of therapeutic procedures for muscular disorders. Several muscle three-dimensional Organ-on-chip models have been developed to measure the generated force. Yet, these technologies require a substantial amount of biological material, which is problematic in the context of limited patient sample. Here we developed a miniaturized 3D myotube culture chip with contraction monitoring capacity. Combination of light-induced molecular adsorption technology and optimized micropatterned substrate design enabled to obtain high culture yields in tightly controlled physical and chemical microenvironments. Spontaneous twitch contractions in 3D myotubes derived from primary human myoblasts were observed, the generated force was measured and the contraction pattern characterized. In addition, the impact of three-dimensional culture on nuclear morphology was analyzed, confirming the similarity in organization between the obtained 3D myotubes and in vivo myofibers. Our system enabled to model LMNA-related Congenital Muscular Dystrophy (L-CMD) with successful development of mutant 3D myotubes displaying contractile dysfunction. We anticipate that this technology shall be used to study contraction characteristics and evaluate how specific diseases affect muscle organization and force generation. Our downsized model system might allow to substantially improve drug screening capability for therapeutic oriented research.

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