STEM CELL-BASED LUNG-ON-CHIP MODELS

    公开(公告)号:US20210062129A1

    公开(公告)日:2021-03-04

    申请号:US16983850

    申请日:2020-08-03

    申请人: EMULATE, INC.

    IPC分类号: C12M3/06 C12N5/071 C12N5/074

    摘要: An in vitro microfluidic “organ-on-chip” device is described herein that mimics the structure and at least one function of specific areas of the epithelial system in vivo. In particular, a stem cell-based Lung-on-Chip is described. This in vitro microfluidic system can be used for modeling differentiation of cells on-chip into lung cells, e.g., a lung (Lung-On-Chip), bronchial (Airway-On-Chip; small-Airway-On-Chip), alveolar sac (Alveolar-On-Chip), etc., for use in modeling disease states of derived tissue, i.e. as healthy, pre-disease and diseased tissues. Additionally, stem cells under differentiation protocols for deriving (producing) differentiated lung cells off-chips may be seeded onto microfluidic devices at any desired point during the in vitro differentiation pathway for further differentiation on-chip or placed on-chip before, during or after terminal differentiation. Additionally, these microfluidic “stem cell-based Lung-on-Chip” allow identification of cells and cellular derived factors driving disease states in addition to drug testing for diseases, infections and for reducing inflammation effecting lung alveolar and/or epithelial regions. Further, fluidic devices are provided seeded with primary alveolar cells for use in providing a functional Type II and Type I cell layer, wherein Type II cells express and secrete surfactants, such as Surfactant B (Surf B; SP-B) and Surfactant C (Surf C; SP-C), which were detectable at the protein level by antibody staining in Type II cells. A number of uses are contemplated for the devices and cells, including but not limited to, for use under inflammatory conditions, in drug development and testing, and for individualized (personalized) medicine. Moreover, an ALI-M was developed for supporting multiple cell types in co-cultures with functional Type II and Type I cells.

    ADVANCED PULMONARY MODELS
    14.
    发明申请

    公开(公告)号:US20200087628A1

    公开(公告)日:2020-03-19

    申请号:US16692383

    申请日:2019-11-22

    申请人: EMULATE, INC.

    IPC分类号: C12N5/071 B01L3/00 C12N1/20

    摘要: The present invention relates to microfluidic fluidic systems and methods for the in vitro modeling diseases of the lung and small airway. In one embodiment, the invention relates to a system for testing responses of a microfluidic Small Airway-on-Chip infected with one or more infectious agents (e.g. respiratory viruses) as a model of respiratory disease exacerbation (e.g. asthma exacerbation). In one embodiment, this disease model on a microfluidic chip allows for a) the testing of anti-inflammatory and/or anti-viral compounds introduced into the system, as well as b) the monitoring of the participation, recruitment and/or movement of immune cells, including the transmigration of cells. In particular, this system provides, in one embodiment, an in-vitro platform for modeling severe asthma as “Severe Asthma-on-Chip.” In some embodiments, this invention provides a model of viral-induced asthma in humans for use in identifying potentially effective treatments.