Options for modeling the respiratory system: inserts, scaffolds and microfluidic chips

Sedláková, Veronika; Kloučková, Michaela; Garlíková, Zuzana; Vašíčková, Kateřina; Jaroš, Josef; Kandra, Mário; Kotasová, Hana; Hampl, Aleš

doi:10.1016/j.drudis.2019.03.006

Cited by 12 publications

(9 citation statements)

References 90 publications

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“…The development of new therapeutics for these diseases requires advanced organ models that closely recapitulate the complexity of the human lung. Complementary in vitro, ex vivo, and in vivo animal models have been developed to study and understand various pulmonary diseases [ 4 , 5 , 6 , 7 ]. In vitro models (2D cell culture) using epithelial cell lines are high-throughput and robust but are limited by their reliance on cell lines originating from cancer tissue or that have been immortalized.…”

Section: Introductionmentioning

confidence: 99%

A Robust Protocol for Decellularized Human Lung Bioink Generation Amenable to 2D and 3D Lung Cell Culture

Dabaghi

Saraei

Carpio

et al. 2021

Cells

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Decellularization efforts must balance the preservation of the extracellular matrix (ECM) components while eliminating the nucleic acid and cellular components. Following effective removal of nucleic acid and cell components, decellularized ECM (dECM) can be solubilized in an acidic environment with the assistance of various enzymes to develop biological scaffolds in different forms, such as sheets, tubular constructs, or three-dimensional (3D) hydrogels. Each organ or tissue that undergoes decellularization requires a distinct and optimized protocol to ensure that nucleic acids are removed, and the ECM components are preserved. The objective of this study was to optimize the decellularization process for dECM isolation from human lung tissues for downstream 2D and 3D cell culture systems. Following protocol optimization and dECM isolation, we performed experiments with a wide range of dECM concentrations to form human lung dECM hydrogels that were physically stable and biologically responsive. The dECM based-hydrogels supported the growth and proliferation of primary human lung fibroblast cells in 3D cultures. The dECM is also amenable to the coating of polyester membranes in Transwell™ Inserts to improve the cell adhesion, proliferation, and barrier function of primary human bronchial epithelial cells in 2D. In conclusion, we present a robust protocol for human lung decellularization, generation of dECM substrate material, and creation of hydrogels that support primary lung cell viability in 2D and 3D culture systems

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Section: Introductionmentioning

confidence: 99%

A Robust Protocol for Decellularized Human Lung Bioink Generation Amenable to 2D and 3D Lung Cell Culture

Dabaghi

Saraei

Carpio

et al. 2021

Cells

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“…Diseases of the respiratory system, including lung cancer, are one of the major causes of mortality and morbidity worldwide ( Robert Mason et al, 2010 ). In-vitro models that encompass the complexity of the respiratory system are required for a better understanding of cancer pathological processes and foster the development of new treatments ( Sedláková et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Establishment of a Pre-vascularized 3D Lung Cancer Model in Fibrin Gel—Influence of Hypoxia and Cancer-Specific Therapeutics

Kniebs

Luengen

Guenther

et al. 2021

Front. Bioeng. Biotechnol.

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Lung cancer is the most frequently diagnosed cancer worldwide and the one that causes the highest mortality. In order to understand the disease and to develop new treatments, in vitro human lung cancer model systems which imitate the physiological conditions is of high significance. In this study, a human 3D lung cancer model was established that features the organization of a tumor with focus on tumor angiogenesis. Vascular networks were formed by co-culture of human umbilical vein endothelial cells and adipose tissue-derived mesenchymal stem cells (ASC) for 14 days in fibrin. A part of the pre-vascularized fibrin gel was replaced by fibrin gel containing lung cancer cells (A549) to form tri-cultures. This 3D cancer model system was cultured under different culture conditions and its behaviour after treatment with different concentrations of tumor-specific therapeutics was evaluated. The evaluation was performed by measurement of metabolic activity, viability, quantification of two-photon laser scanning microscopy and measurement of the proangiogenic factor vascular endothelial growth factor in the supernatant. Hypoxic conditions promoted vascularization compared to normoxic cultured controls in co- and tri-cultures as shown by significantly increased vascular structures, longer structures with a higher area and volume, and secretion of vascular endothelial growth factor. Cancer cells also promoted vascularization. Treatment with 50 µM gefitinib or 50 nM paclitaxel decreased the vascularization significantly. VEGF secretion was only reduced after treatment with gefitinib, while in contrast secretion remained constant during medication with paclitaxel. The findings suggest that the herein described 3D lung cancer model provides a novel platform to investigate the angiogenic potential of cancer cells and its responses to therapeutics. Thus, it can serve as a promising approach for the development and patient-specific pre-selection of anticancer treatment.

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“…Many such in vitro models include tissue models of skin, glomerular filtration units as well as alveolar-capillary barrier models. 43 − 48 A natural polymer, laminin I, extracted from murine has been electrospun to produce nanofibrous scaffolds that mimic BM in aspects of morphology including fiber diameter, pore size as well as architecture. Unlike electrospun biopolymers including collagen and fibronectin, laminin does not require cross-linking modification steps to maintain its fibrous morphology when exposed to an aqueous environment.…”

Section: Electrospun Bm Mimicsmentioning

confidence: 99%

“…To reach the goal of a native-like scaffold, a wide variety of different biomaterials have been synthesized and manufactured, which feature typical BM properties such as intricate fibrillar architecture, the viscoelastic mechanical properties, the adhesive sequences, the dynamic enzyme-induced nature as well as the possibility of controlled storage and release of bioactive substances such as growth factors. 33 , 35 − 43 These biomaterials are mostly fabricated from natural and synthetic polymer systems and try to combine multiple BM properties that are tailored toward the needs of a desired tissue construct or a region of interest. 44 Scaffolds are used to construct in vitro models that are valuable research tools for unraveling fundamental biological processes involved in tissue homeostasis and disease development as well as serving as industrial platforms for drug screening.…”

Section: Introductionmentioning

confidence: 99%

Mimicking the Natural Basement Membrane for Advanced Tissue Engineering

et al. 2022

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Advancements in the field of tissue engineering have led to the elucidation of physical and chemical characteristics of physiological basement membranes (BM) as specialized forms of the extracellular matrix. Efforts to recapitulate the intricate structure and biological composition of the BM have encountered various advancements due to its impact on cell fate, function, and regulation. More attention has been paid to synthesizing biocompatible and biofunctional fibrillar scaffolds that closely mimic the natural BM. Specific modifications in biomimetic BM have paved the way for the development of in vitro models like alveolar-capillary barrier, airway models, skin, blood-brain barrier, kidney barrier, and metastatic models, which can be used for personalized drug screening, understanding physiological and pathological pathways, and tissue implants. In this Review, we focus on the structure, composition, and functions of in vivo BM and the ongoing efforts to mimic it synthetically. Light has been shed on the advantages and limitations of various forms of biomimetic BM scaffolds including porous polymeric membranes, hydrogels, and electrospun membranes This Review further elaborates and justifies the significance of BM mimics in tissue engineering, in particular in the development of in vitro organ model systems.

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Options for modeling the respiratory system: inserts, scaffolds and microfluidic chips

Cited by 12 publications

References 90 publications

A Robust Protocol for Decellularized Human Lung Bioink Generation Amenable to 2D and 3D Lung Cell Culture

A Robust Protocol for Decellularized Human Lung Bioink Generation Amenable to 2D and 3D Lung Cell Culture

Establishment of a Pre-vascularized 3D Lung Cancer Model in Fibrin Gel—Influence of Hypoxia and Cancer-Specific Therapeutics

Mimicking the Natural Basement Membrane for Advanced Tissue Engineering

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