Abstract: There is provided a polymeric microsphere comprising a thermally responsive monomer crosslinked with a functional group monomer, wherein the functional group monomer comprises at least one of a carboxylic acid functional group or an amine functional group. The thermally responsive monomer is preferably N-isopropylacrylamide (NIPAM), and the microspheres preferably comprise a coating of polymerized catecholamines (e.g. DOPA). There is also provided a method of preparing the polymeric microsphere and uses of the polymeric microsphere in culturing, harvesting, or expanding stem cells or stromal cells. Preferably, the cells, e.g. hMSCs (human mesenchymal stem/stromal cells), are expanded or harvested in serum-free and xeno-free medium.

Abstract: A method and system for predicting liver injury in vivo due to hepatocyte damage by a test compound are provided. The method includes acquiring images of fluorescently stained cells obtained from a cell culture in which the cells have been treated with a dose-range of at least the test compound and its vehicle. The cells may be hepatic cells including primary or immortalized hepatocytes, hepatoma cells or induced pluripotent stem cell-derived hepatocyte-like cells. The acquired images are segmented. The method further includes extracting and analyzing one or more phenotypic features from the segmented images, wherein the one or more phenotypic features are selected from the group of intensity, textural, morphological, or ratiometric features consisting of (a) features of DNA, (b) features of RELA (NF-KB p65), and (c) features of actin filaments at different subcellular regions and d) features of cellular organelles and their substructures in the segmented images.

Abstract: A method and system for predicting liver injury in vivo due to hepatocyte damage by a test compound are provided. The method includes acquiring images of fluorescently stained cells obtained from a cell culture in which the cells have been treated with a dose-range of at least the test compound and its vehicle. The cells may be hepatic cells including primary or immortalized hepatocytes, hepatoma cells or induced pluripotent stem cell-derived hepatocyte-like cells. The acquired images are segmented. The method further includes extracting and analyzing one or more phenotypic features from the segmented images, wherein the one or more phenotypic features are selected from the group of intensity, textural, morphological, or ratiometric features consisting of (a) features of DNA, (b) features of RELA (NF-KB p65), and (c) features of actin filaments at different subcellular regions and d) features of cellular organelles and their substructures in the segmented images.

Abstract: The present invention provides methods for the prediction of in vivo cell-specific toxicity of a compound that combines high-throughput imaging of cultured cells, quantitative phenotypic profiling, and machine learning methods. More particularly, the invention provides a method for the prediction of in vivo renal proximal tubular-, bronchial-epithelial-, and alveolar-cell-specific toxicities of a soluble or particulate compound that comprises contacting cultured human kidney and pulmonary cells with the compound at a range of concentrations, then labeling the cells with DNA, ?H2AX and actin markers and obtaining textural features, spatial correlation features, ratios of the markers, intensity features, cell count and morphology, estimating dose response curves and performing automatic classification of the compound using a random-forest algorithm.

Abstract: There is provided a polymeric microsphere comprising a thermally responsive monomer crosslinked with a functional group monomer, wherein the functional group monomer comprises at least one of a carboxylic acid functional group or an amine functional group. The thermally responsive monomer is preferably N-isopropylacrylamide (NIPAM), and the microspheres preferably comprise a coating of polymerized catecholamines (e.g. DOPA). There is also provided a method of preparing the polymeric microsphere and uses of the polymeric microsphere in culturing, harvesting, or expanding stem cells or stromal cells. Preferably, the cells, e.g. hMSCs (human mesenchymal stem/stromal cells), are expanded or harvested in serum-free and xeno-free medium.

Abstract: There is provided a method of differentiating an induced pluripotent stem cell (iPSC) into a renal proximal tubular cell (PTC)-like cell. The method comprises culturing an undifferentiated iPSC in a renal epithelial cell culture medium in the presence of one or more extracellular matrix (ECM) molecules, bone morphogenic protein 2 (BMP2) and bone morphogenic protein 7 (BMP7), for a period of from about 8 to about 10 days, under conditions sufficient to induce differentiation of the iPSC into a PTC-like cell. A cell population of differentiated PTC-like cells is also provided, as well as uses and methods of use of the cell population.

Abstract: There is provided a method for culturing a stem cell in vitro. The method comprises providing a substrate surface coated with a coating comprising a molecule having a catechol moiety or a polymer thereof; and growing a stem cell on said coated substrate surface in a growth medium.

Abstract: There is provided a bioreactor device having cells, including human primary proximal tubule cells (HPTCs) or HPTC-like cells on the exterior surface of hollow fiber membranes included within the device. Also provided are bioartificial kidney devices incorporate the bioreactor device and methods of using such devices.

Abstract: There is provided a method of screening for toxicity of a compound. The method comprises contacting a test compound with a test population of cells in which nuclear factor (NF)-?B has not been activated prior to the contacting; determining nuclear localization levels of NF-?B in the test population subsequent to the contacting; and comparing nuclear localization levels of NF-?B of a control population that has not been contacted with the test compound. An increase in nuclear localization levels of NF-?B as of the test population relative to the control population is indicative that the test compound injures the cells and/or induces a pro-inflammatory response and thus is toxic to the cell type used in the method.

Abstract: There is provided an in vitro assay for screening a test compound for toxicity in renal proximal tubular cells. The method comprises contacting a test compound with a test population of renal proximal tubular cells; and examining one or more cell morphology features, examining one or more cytoskeleton features, and/or determining cell numbers of the renal proximal tubular cells in the test population and comparing such cell morphology, arrangement of cytoskeletal components and/or cell count with the respective features of a control population. A change in one or more cell morphology features, a change in arrangement of one or more cytoskeleton features or a decrease in cell numbers of the test population relative to the control population is indicative that the test compound is toxic for renal proximal tubular cells.

Abstract: There is provided a method of differentiating an induced pluripotent stem cell (iPSC) into a renal proximal tubular cell (PTC)-like cell. The method comprises culturing an undifferentiated iPSC in a renal epithelial cell culture medium in the presence of one or more extracellular matrix (ECM) molecules, bone morphogenic protein 2 (BMP2) and bone morphogenic protein 7 (BMP7), for a period of from about 8 to about 10 days, under conditions sufficient to induce differentiation of the iPSC into a PTC-like cell. A cell population of differentiated PTC-like cells is also provided, as well as uses and methods of use of the cell population.

Abstract: The present invention generally relates to modified substrates such as membranes for use in bioartificial organs, such as bioartificial kidneys, and other applications. Certain aspects are generally directed to a membrane or other substrate modified to facilitate the attachment of cells. In one set of embodiments, the substrate or membrane may be at least partially coated with an adhesive such as 3,4-dihydroxy-L-phenylalanine (DOPA), poly(dopamine), or other adhesive comprising a molecule having a catechol moiety, for example on one side of the membrane or substrate. On at least a portion of the adhesive coated portion of the substrate, a protein may be coated, such as an extracellular matrix protein (for example, a collagen), to which cells such as primary human renal proximal tubule cells may be adhered. Surprisingly, such a dual coating may be used to promote the attachment of such cells to a membrane or other substrate that otherwise may not promote cell adhesion.

Abstract: There is provided an in vitro assay for screening a test compound for toxicity in renal proximal tubular cells. The method comprises contacting a test compound with a test population of renal proximal tubular cells; and examining one or more cell morphology features, examining one or more cytoskeleton features, and/or determining cell numbers of the renal proximal tubular cells in the test population and comparing such cell morphology, arrangement of cytoskeletal components and/or cell count with the respective features of a control population. A change in one or more cell morphology features, a change in arrangement of one or more cytoskeleton features or a decrease in cell numbers of the test population relative to the control population is indicative that the test compound is toxic for renal proximal tubular cells.

Abstract: There is provided an in vitro assay for screening a test compound for toxicity in renal proximal tubular cells. The method comprises contacting a test compound with a test population of renal proximal tubular cells; and determining the expression level of an interleukin in the test population, the interleukin being interleukin-6 (IL-6) or interleukin-8 (IL-8), or both. Expression levels of the interleukin in the test population being greater than expression levels in a control population of renal proximal tubular cells not contacted with the test compound is indicative that the test compound is toxic for renal proximal tubular cells.

Abstract: There is provided a method for culturing a stem cell in vitro. The method comprises providing a substrate surface coated with a coating comprising a molecule having a catechol moiety or a polymer thereof; and growing a stem cell on said coated substrate surface in a growth medium.

Abstract: There is provided a bioreactor device having cells, including human primary proximal tubule cells (HPTCs) or HPTC-like cells on the exterior surface of hollow fiber membranes included within the device. Also provided are bioartificial kidney devices incorporate the bioreactor device and methods of using such devices.

Abstract: The present invention generally relates to delivery of BMP-7 or functional variants or functional fragments thereof and/or a BMP-7 agonist and methods of use thereof. In some embodiments, methods and devices are provided for delivery of BMP-7 or functional variants or functional fragments thereof and/or a BMP-7 agonist to a patient. In some cases, the BMP-7 or functional variants or functional fragments thereof and/or a BMP-7 agonist may be released in controlled fashion from a device in fluid communication with a patient. In some embodiments, the BMP-7 or functional variants or functional fragments thereof and/or a BMP-7 agonist may be expressed by cells within a device. In other embodiments, methods are provided for improving the function of devices containing renal proximal tubule cells.

Abstract: The present invention generally relates to modified substrates such as membranes for use in bioartificial organs, such as bioartificial kidneys, and other applications. Certain aspects are generally directed to a membrane or other substrate modified to facilitate the attachment of cells. In one set of embodiments, the substrate or membrane may be at least partially coated with an adhesive such as 3,4-dihydroxy-L-phenylalanine (DOPA), poly(dopamine), or other adhesive comprising a molecule having a catechol moiety, for example on one side of the membrane or substrate. On at least a portion of the adhesive coated portion of the substrate, a protein may be coated, such as an extracellular matrix protein (for example, a collagen), to which cells such as primary human renal proximal tubule cells may be adhered. Surprisingly, such a dual coating may be used to promote the attachment of such cells to a membrane or other substrate that otherwise may not promote cell adhesion.

Abstract: There is provided a method of making a renal tubule. The method comprises seeding renal tubule cells onto a solid surface; culturing the renal tubule cells in a liquid growth medium to form a monolayer on the solid surface; and continuing culturing the renal tubule cells to form a tubule.