Abstract: There is provided a method of assessing fibrosis in a tissue sample. The method includes: obtaining a stained image of a stained tissue sample, the stained tissue sample being stained in relation to collagen therein; producing a plurality of different types of collagen images based on the stained image, the plurality of different types of collagen images corresponding to a plurality of different types of collagen, respectively; determining a plurality of different types of collagen parameters based on the plurality of different types of collagen images using a deep neural network; and determining a degree of fibrosis in the stained tissue sample based on the plurality of different types of collagen parameters. The plurality of different types of collagen comprises portal collagen, fibrillary collagen and septal collagen.

Abstract: The present invention relates to a digital CRISPR-based method for detecting and quantitating target nucleic acids in a sample comprising: forming a mixture comprising sample nucleic acids; isothermal amplification reaction reagents for amplifying one or more target nucleic acid sequences; partitioning the mixture into a plurality of compartments; incubating the partitioned mixture at a temperature for isothermal amplification and Cas effector cleavage of an amplified DNA strand, detecting a signal from cleavage of the non-target sequence, thereby detecting the one or more target sequences in the sample, and determining the copy number of the target nucleic acid based on a Poisson distribution of the proportion of positive-to-negative compartments. The invention also relates to a method for detecting presence and/or of a disease in a subject, and a kit to quantitate nucleic acids in a sample.

Abstract: The invention relates to treating a plant-based material with an agent and/or a force to enable the plant-based material to mimic the colour of animal products, wherein the agent and/or force is capable of controlled permeabilisation of cell membrane to thereby release polyphenols from the cells of the plant-based material to allow polyphenol-cell wall interaction and/or causes the oxidation of polyphenols in the plant-based material. Also disclosed is a plant-based food product, such as plant-based meat substitutes, produced by the process thereof.

Abstract: The invention relates to a method of producing an iPSC-derived Kupffer Cell (IKC). The method may comprise providing a macrophage precursor (preMcp) derived from an induced pluripotent stem cell (iPSC). The macrophage precursor (preM-cp) may be cultured in the presence of a hepatic cue, such as a combination of primary human hepatocyte conditioned media and Advanced DMEM, thereby obtaining the iPSC-derived Kupffer Cell. The iPSC-derived Kupffer Cell may display a biological property of a primary Kupffer cell, such as a primary adult human KC (pKC). The biological activity comprises expression of a macrophage marker such as CD11, CD14, CD68, CD163, CD32, CLEC-4F, ID1 and ID3.

Abstract: There is provided a method of assessing fibrosis in a tissue sample. The method includes: obtaining a stained image of a stained tissue sample, the stained tissue sample being stained in relation to collagen therein; producing a plurality of different types of collagen images based on the stained image, the plurality of different types of collagen images corresponding to a plurality of different types of collagen, respectively; determining a plurality of different types of collagen parameters based on the plurality of different types of collagen images using a deep neural network; and determining a degree of fibrosis in the stained tissue sample based on the plurality of different types of collagen parameters. The plurality of different types of collagen comprises portal collagen, fibrillary collagen and septal collagen.

Abstract: The present disclosure provides a method of deriving hepatic macrophages from stem cell-derived monocytes, through the use of hepatic macrophage culture medium comprising a hepatocyte conditioned medium and a basal medium, wherein the conditioned medium is obtained through culturing hepatocytes in a serum-free culture medium in the presence of an extracellular matrix. Also disclosed is a kit used for such a method and hepatic macrophages derived using the method and uses thereof.

Abstract: Disclosed are methods of differentiating stem cells in order to obtain hepatocyte-like cells, the method comprising the steps of a) subjecting definitive endoderm to at least one epigenetic modulator to obtain hepatoblasts and b) subjecting the hepatoblasts to at least one stem cell differentiation pathway inhibitor to obtain hepatocyte-like cells; wherein steps a) and b) do not comprise the use of a growth factor. In one preferred embodiment, the epigenetic modulator may be sodium butyrate and/or DMSO and the stem cell differentiation pathway inhibitor may be SB431542 and/or DMSO. Also disclosed are hepatocyte-like cells obtained from the method and uses of these cells such as drug screening.

Abstract: A method for determining a stage of fibrosis in a liver is disclosed. The method comprises the steps of: (1a) obtaining input data relating to the liver, the input data being generated using a second harmonic generation based imaging system; (1b) identifying a plurality of morphological features of the liver from the input data relating to the liver; (1c) generating a plurality of measurements based on the identified plurality of morphological features; and (1d) determining the stage of fibrosis in the liver based, on the generated plurality of measurements.

Abstract: A method and system of in vitro developmental toxicity testing comprising the steps of micropatterning an extracellular matrix; growing embryonic stem cells on the micropatterned extracellular matrix in the presence of mesoendodermal induction and testing for change of the geometrical mesoendoderm structure in the presence or absence of a test compound wherein (1) a decrease in mesoendodermal differentiation and/or (2) a change in morphology of the geometrical mesoendoderm structure in the presence of the test compound compared to cells in the absence of the test compound indicates that the test compound is a developmental toxic agent.

Abstract: An imaging system is provided that includes a pulsed light source providing pulsed light and is applicable to both microscopes and endoscopes. One or more optical elements with certain dispersive properties are positioned to receive the pulsed light and apply selective dispersive properties to shift the focal plane according to the user and to produce two photon (2p) wide field uniform illumination and 2p wide field structured illumination for the purpose of improving the optical axial resolution and rejection of background signal. An imaging element receives the signal arising from the 2p wide field uniform illumination and 2p wide field structured illumination and produces a respective 3D resolved image of a sample.

Abstract: Disclosed are methods of differentiating stem cells in order to obtain hepatocyte-like cells, the method comprising the steps of a) subjecting definitive endoderm to at least one epigenetic modulator to obtain hepatoblasts and b) subjecting the hepatoblasts to at least one stem cell differentiation pathway inhibitor to obtain hepatocyte-like cells; wherein steps a) and b) do not comprise the use of a growth factor. In one preferred embodiment, the epigenetic modulator may be sodium butyrate and/or DMSO and the stem cell differentiation pathway inhibitor may be SB431542 and/or DMSO. Also disclosed are hepatocyte-like cells obtained from the method and uses of these cells such as drug screening.

Abstract: A method for assessing fibrosis in a tissue is proposed. The method uses a test image which is an image of the tissue and comprises identifying, from the test image, a portal collagen area, a septal collagen area and a fibrillar collagen area respectively comprising pixels representing portal collagen, septal collagen and fibrillar collagen of the tissue, obtaining quantitative values of one or more features for each identified area based on characteristics of the identified area in the test image and assessing fibrosis using the quantitative values obtained for all the identified areas.

Abstract: The invention provides a surface, wherein said surface comprises (i) a polymer substrate and (ii) sugar groups and peptide groups coupled to said substrate suitable for culturing hepatocytes.

Abstract: The invention relates to an apparatus (1) for culturing anchorage-dependent cells. The apparatus (1) comprises a housing (2) with an inlet (4) and an outlet (5), and a plurality of culture plates (6) removably stacked within the housing (2). The housing (2) has a circumferential wall (7), a base (8) and a top wall (9). The base (8) comprises the inlet (4) and the top wall (9) comprises the outlet (5). The circumferential wall (7) of the housing (2) defines a longitudinal axis thereof, as well as an inner cross section perpendicular to the longitudinal axis. Shape and dimensions of the inner cross section are essentially uniform along the longitudinal axis. The culture plates (6) are arranged at least essentially parallel to each other. Each plate (6) is mounted and sealed to the circumferential wall (7) of the housing (2). Plates (6) are arranged at a distance from each other. Each culture plate (6) has a through hole (14), so that inlet (4) and outlet (5) are in fluid communication.

Abstract: A method for assessing fibrosis in a tissue is proposed. The method uses a test image which is an image of the tissue and comprises identifying, from the test image, a portal collagen area, a septal collagen area and a fibrillar collagen area respectively comprising pixels representing portal collagen, septal collagen and fibrillar collagen of the tissue, obtaining quantitative values of one or more features for each identified area based on characteristics of the identified area in the test image and assessing fibrosis using the quantitative values obtained for all the identified areas.

Abstract: A method of culturing cells or tissues is provided. The method comprises a) providing a support, wherein the support is an optical medium with a patterned surface; b) contacting the support with cells and a culture medium; and c) culturing the cells under suitable cultivation conditions. A device for cell or tissue culture comprising an optical medium, wherein a patterned surface of the optical medium forms a support upon which cells are cultivated, is also provided.

Abstract: A method and system of in vitro developmental toxicity testing comprising the steps of micropatterning an extracellular matrix; growing embryonic stem cells on the micropatterned extracellular matrix in the presence of mesoendermal induction and testing for change of the geometrical mesoendoderm structure in the presence or absence of a test compound wherein (1) a decrease in mesoendodermal differentiation and/or (2) a change in morphology of the geometrical mesoendoderm structure in the presence of the test compound compared to cells in the absence of the test compound indicates that the test compound is a developmental toxic agent.

Abstract: A microfluidic continuous flow device comprising a channel which comprises a first and a second area wherein the first area of the channel is a compartment which is defined by partitioning elements and the second area of the channel is a space outside the compartment; wherein through passages which are formed between the partitioning elements are dimensioned such as to retain a biological material and optionally a sustained release composition which can be comprised in the compartment within the compartment; wherein the channel has a first inlet to the compartment through which biological material can be introduced into the compartment; a second inlet for introducing a cultivation medium into a space of the channel arranged outside of the compartment, and an outlet. The present invention further refers to methods of using the devices of the present invention and kits comprising the microfluidic continuous flow devices of the present invention.

Abstract: Scaffold comprises a polymer defining macropores and comprising hydroxypropylcellulose partially substituted by a substituent comprising a self-crosslinkable group, which is crosslinked through the self-crosslinkable group. The macropores have an average pore size larger than 50 microns and are at least partially interconnected. In one method, bicontinuous emulsion comprising a continuous aqueous phase and a continuous polymer phase is formed. The polymer phase comprises hydroxypropylcellulose partially substituted by a substituent comprising a self-crosslinkable group, and is crosslinked through the self-crosslinkable group to form a polymer defining at least partially interconnected pores. In another method, phase separation is induced in a solution comprising a polymer precursor and water to form a bicontinuous emulsion comprising a continuous polymer phase and a continuous aqueous phase.

Abstract: An imaging system is provided that includes a pulsed light source providing pulsed light and is applicable to both microscopes and endoscopes. One or more optical elements with certain dispersive properties are positioned to receive the pulsed light and apply selective dispersive properties to shift the focal plane according to the user and to produce two photon (2p) wide field uniform illumination and 2p wide field structured illumination for the purpose of improving the optical axial resolution and rejection of background signal. An imaging element receives the signal arising from the 2p wide field uniform illumination and 2p wide field structured illumination and produces a respective 3D resolved image of a sample.