Novel three-dimensional biochip pulmonary sarcoidosis model

Calcagno, Tess Moore; Zhang, Chongxu; Tian, Rong; Ebrahimi, Babak; Mirsaeidi, Mehdi

doi:10.1371/journal.pone.0245805

Cited by 4 publications

(4 citation statements)

References 38 publications

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“…Monitoring secretion of cytokines in a biochip of pulmonary sarcoidosis model [230]. (b) Measurement of metabolic activity following deposition of PM-like particles in airway-on chip platforms [148].…”

Section: Discussionmentioning

confidence: 99%

Advanced human-relevant in vitro pulmonary platforms for respiratory therapeutics

Artzy‐Schnirman

Raviv

Flikshtain

et al. 2021

Advanced Drug Delivery Reviews

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Over the past years, advanced in vitro pulmonary platforms have witnessed exciting developments that are pushing beyond traditional preclinical cell culture methods. Here, we discuss ongoing efforts in bridging the gap between in vivo and in vitro interfaces and identify some of the bioengineering challenges that lie ahead in delivering new generations of human-relevant in vitro pulmonary platforms. Notably, in vitro strategies using foremost lung-on-chips and biocompatible "soft" membranes have focused on platforms that emphasize phenotypical endpoints recapitulating key physiological and cellular functions. We review some of the most recent in vitro studies underlining seminal therapeutic screens and translational applications and open our discussion to promising avenues of pulmonary therapeutic exploration focusing on liposomes. Undeniably, there still remains a recognized trade-off between the physiological and biological complexity of these novel in vitro lung models and their ability to deliver assays with throughput capabilities. The upcoming years are thus anticipated to see further developments in broadening the applicability of such in vitro systems and accelerating therapeutic exploration for drug discovery and translational medicine in treating respiratory disorders.

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Section: Discussionmentioning

confidence: 99%

Advanced human-relevant in vitro pulmonary platforms for respiratory therapeutics

Artzy‐Schnirman

Raviv

Flikshtain

et al. 2021

Advanced Drug Delivery Reviews

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“…The 3D-BSGM Model [ 9 ] was used to test the hypothesis that α-MSH reduces inflammatory cytokines in an integrated granuloma model with a lung biochip. Our previous study developed a new integrated LOMM and granuloma called 3D-BSGM using PMBCs exposed to MAB microparticles to create a human sarcoid-like granulomas Field [ 9 ] effectively. This study used MAB microparticles to develop 3D-BSGM human sarcoid-like granulomas (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In the meantime, we also developed ALI from NBECs and human endothelial cells as described in the LOMM development above [ 7 ]. A little scratch was made on the ALI of the LOMM, and then 50 μL of the developed granulomas from PBMCs (2 × 10 6 cells) were added to ALI on the microchip to develop 3D-BSGM as described elsewhere [ 9 ]. We designed 3 groups for this experiment: control (LOMM + unchallenged PBMCs), 3D-BSGM (LOMM + challenged PBMCs + saline as treatment), and 3D-BSGM + α-MSH (LOMM + challenged PBMCs + α-MSH as treatment).…”

Section: Methodsmentioning

confidence: 99%

Anti-inflammatory Properties of the Alpha-Melanocyte-Stimulating Hormone in Models of Granulomatous Inflammation

Shahraki

Tian

Zhang

et al. 2022

Lung

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Purpose Alpha-melanocyte stimulating hormone (α-MSH) is known to have anti-inflammatory effects. However, the anti-inflammatory properties of α-MSH on normal bronchial epithelial cells are largely unknown, especially in the context of in vitro sarcoidosis models. Methods We evaluated the anti-inflammatory effects of α-MSH on two different in vitro sarcoidosis models (lung-on-membrane model; LOMM and three-dimensional biochip pulmonary sarcoidosis model; 3D-BSGM) generated from NBECs and an in vivo sarcoidosis mouse model. Results Treatment with α-MSH decreased inflammatory cytokine levels and downregulated type I interferon pathway genes and related proteins in LOMM and 3D-BSGM models. Treatment with α-MSH also significantly decreased macrophages and cytotoxic T-cells counts in a sarcoidosis mice model. Conclusion Our results confirm the direct role of type I IFNs in the pathogenesis of sarcoid lung granulomas and highlight α-MSH as a potential novel therapeutic agent for treating pulmonary sarcoidosis. Graphical Abstract

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“…Furthermore, this vacuum moves the membrane and induces stretching of the cellular layer, enabling long term functional culture of the lung model. Such innovative bioengineered LOAC in vitro models hold future promises for understanding abnormal pulmonary homeostasis and assessing therapeutic strategies in the pulmonary diseases ( 191 , 192 ). Of note, LOAC models are used do simulate early Mycobacterium tuberculosis infection of the lung and reproduces complex integrated organ-level responses to bacteria and inflammatory cytokines released into the alveolar space ( 193 ).…”

Section: In Vitro Models Of Pulmonary Inflammation and Barri...mentioning

confidence: 99%

A Barrier to Defend - Models of Pulmonary Barrier to Study Acute Inflammatory Diseases

et al. 2022

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Pulmonary diseases represent four out of ten most common causes for worldwide mortality. Thus, pulmonary infections with subsequent inflammatory responses represent a major public health concern. The pulmonary barrier is a vulnerable entry site for several stress factors, including pathogens such as viruses, and bacteria, but also environmental factors e.g. toxins, air pollutants, as well as allergens. These pathogens or pathogen-associated molecular pattern and inflammatory agents e.g. damage-associated molecular pattern cause significant disturbances in the pulmonary barrier. The physiological and biological functions, as well as the architecture and homeostatic maintenance of the pulmonary barrier are highly complex. The airway epithelium, denoting the first pulmonary barrier, encompasses cells releasing a plethora of chemokines and cytokines, and is further covered with a mucus layer containing antimicrobial peptides, which are responsible for the pathogen clearance. Submucosal antigen-presenting cells and neutrophilic granulocytes are also involved in the defense mechanisms and counterregulation of pulmonary infections, and thus may directly affect the pulmonary barrier function. The detailed understanding of the pulmonary barrier including its architecture and functions is crucial for the diagnosis, prognosis, and therapeutic treatment strategies of pulmonary diseases. Thus, considering multiple side effects and limited efficacy of current therapeutic treatment strategies in patients with inflammatory diseases make experimental in vitro and in vivo models necessary to improving clinical therapy options. This review describes existing models for studyying the pulmonary barrier function under acute inflammatory conditions, which are meant to improve the translational approaches for outcome predictions, patient monitoring, and treatment decision-making.

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Novel three-dimensional biochip pulmonary sarcoidosis model

Cited by 4 publications

References 38 publications

Advanced human-relevant in vitro pulmonary platforms for respiratory therapeutics

Advanced human-relevant in vitro pulmonary platforms for respiratory therapeutics

Anti-inflammatory Properties of the Alpha-Melanocyte-Stimulating Hormone in Models of Granulomatous Inflammation

A Barrier to Defend - Models of Pulmonary Barrier to Study Acute Inflammatory Diseases

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