BRAIN-CHIP MODELING NEURODEGENERATION AND NEUROINFLAMMATION IN PARKINSON'S DISEASE

    公开(公告)号:US20220340849A1

    公开(公告)日:2022-10-27

    申请号:US17719627

    申请日:2022-04-13

    申请人: EMULATE, INC.

    摘要: The invention relates to modeling brain neuronal disease in a microfluidic device, comprising a co-culture of iPS-derived brain endothelial cells; iPS-derived dopaminergic neurons; primary microglia; and primary astrocytes, a Blood-Brain-Barrier (BBB)-Chip and a Brain-Chip. In particular, cross-talk between glial cells (e.g. microglia and astrocytes) with neuronal cells, in further contact with endothelial cells is contemplated for use for identifying drug targets under conditions for inducing in vivo relevant neuronal inflammation, neurodegeneration and neuronal death. Thus, in one embodiment, a microfluidic Brain-Chip comprising a co-culture of brain cells is exposed to α-synuclein preformed fibrils (PFF), a type of pathogenic form of α-synuclein. Such α-synuclein PFF exposure demonstrates an in vivo relevant disease pathogenesis on a microfluidic device as a concentration- and time-controlled manner that may be used for preclinical drug evaluation for diseases related to neuronal inflammation, e.g. Parkinson's disease (PD). In some embodiments, modulation of complement in the presence of neuronal inflammation is contemplated. In some embodiments, drug delivery to brain cells across the BBB is contemplated for preclinical testing of drug efficacy for slowing or stopping neuronal inflammation and degeneration.

    In vitro gastrointestinal model comprising lamina propria-derived cells

    公开(公告)号:US11230688B2

    公开(公告)日:2022-01-25

    申请号:US15820011

    申请日:2017-11-21

    申请人: EMULATE, Inc.

    摘要: An in vitro microfluidic gut-on-chip is described herein that mimics the structure and at least one function of specific areas of the gastrointestinal system in vivo. In particular, a multicellular, layered, microfluidic culture is described, allowing for interactions between lamina propria-derived cells and gastrointestinal epithelial cells and endothelial cells. This in vitro microfluidic system can be used for modeling inflammatory gastrointestinal tissue, e.g., Crohn's disease, colitis and other inflammatory gastrointestinal disorders. These multicellular, layered microfluidic gut-on-chip further allow for comparisons between types of gastrointestinal tissues, e.g., small intestinal deuodejeum, small intestinal ileium, large intestinal colon, etc., and between disease states of gastrointestinal tissue, i.e. healthy, pre-disease and diseased areas. Additionally, these microfluidic gut-on-chips allow identification of cells and cellular derived factors driving disease states and drug testing for reducing inflammation.

    IN VITRO EPITHELIAL MODELS COMPRISING LAMINA PROPRIA-DERIVED CELLS

    公开(公告)号:US20180185844A1

    公开(公告)日:2018-07-05

    申请号:US15819435

    申请日:2017-11-21

    申请人: EMULATE, Inc.

    IPC分类号: B01L3/00 G01N33/50

    摘要: An in vitro microfluidic “organ-on-chip” is described herein that mimics the structure and at least one function of specific areas of the epithelial system in vivo. In particular, a multicellular, layered, microfluidic culture is described, allowing for interactions between lamina propria-derived cells and the associated tissue specific epithelial cells and endothelial cells. This in vitro microfluidic system can be used for modeling inflammatory tissue, e.g., autoimmune disorders involving epithelia and diseases involving epithelial layers. These multicellular, layered microfluidic “organ-on-chip”, e.g. “epithelia-on-chip” further allow for comparisons between types of epithelia tissues, e.g., lung (Lung-On-Chip), bronchial (Airway-On-Chip), skin (Skin-On-Chip), cervix (Cervix-On-Chip), blood brain barrier (BBB-On-Chip), etc., in additional to neurovascular tissue, (Brain-On-Chip), and between different disease states of tissue, i.e. healthy, pre-disease and diseased areas. Additionally, these microfluidic “organ-on-chips” allow identification of cells and cellular derived factors driving disease states in addition to drug testing for reducing inflammation effecting epithelial regions.