Provided are embryonic stem (ES) cell-derived tissue modeling systems. In particular, systems for the de novo generation of tissue by parallel drug selection of cell types constituting the tissue of interest in one culture of differentiating ES cells is described as well as the use of such systems in transplantation and drug development.

In certain aspects the present invention provides engineered neural cells, neural stem cells, or neural progenitor cells that contain a nucleotide sequence that encodes an adenovirus E40RF1 polypeptide and/or that contain an adenovirus E40RF1 polypeptide. The present invention also provides methods of making and using such engineered cells and compositions comprising such engineered cells.

Described herein is a microphysiological system for models of disease. Specifically, induced pluripotent stem cells (iPSCs) and iPSC-derived cells, including those obtained from disease patients, are seeded onto microfluidic chip devices to study cellular development and disease pathogenesis. Herein, neurodegenerative disease modeling, including Parkinson's Disease (PD) is shown to reproduce key PD pathology in a vascularized human model that contains neurons relating to PD pathology. Such compositions and methods are used for research for PD biomarkers, patient screening for PD risk assessment, and therapeutic discovery and testing. A panel of biomarkers are generated through analysis of living PD-chips by neural activity, whole transcriptomic, proteomic, and metabolomic analysis, and functional enzyme tests of media and tissue. Introducing therapeutics through a vasculature channel, coupled with blood brain barrier penetration studies can be assessed for efficacy in the human neural cells present in the PD-Chip.

The invention relates to scaffold-free three dimensional nerve fibroblast constructs and method of generating the nerve fibroblast constructs. The invention also relates to methods or repairing nerve transection and replacing damaged nerve tissue using the nerve fibroblast constructs of the invention.

The present invention relates to the field of in vitro 3D modeling of neural tissues, particularly of the brain. There is the need of developing cell culture models of neural tissue that reflect physiological aspects of neural tissues. The present invention provides bioengineered neuronal organoid (BENOs) compositions capable of organizing as a functional neuronal network and methods for modeling a disease of neural tissue and/or for drug design based on phenotypic tissue screening or phenotypic drug screening using the disclosed BENO compositions. The present invention also relates to kits for making the instant BENO compositions.

A method for evaluating activity of a test substance for inhibiting or promoting aggregation of aggregating proteins is provided. The method includes culturing cells in the presence of aggregating proteins labeled with a label and a test substance, thereby forming a cell culture and quantifying aggregated and/or deposited aggregating proteins on a surface of the cells and/or in the cells in the cell culture with the use of the label as an indicator.

The invention relates to culturing brain endothelial cells, and optionally astrocytes and neurons in a fluidic device under conditions whereby the cells mimic the structure and function of the blood brain barrier. Culture of such cells in a microfluidic device, whether alone or in combination with other cells, drives maturation and/or differentiation further than existing systems.

What is provided is a nervous system cell-containing spheroid having suitable drug responsiveness. There are provided a nervous system cell-containing spheroid including at least one kind of nerve cells and nervous system cells other than the nerve cells, in which the proportion of the volume of one cell layer positioned at an outer edge of the spheroid to the volume of the entire spheroid is 15% to 30%; a method for producing the nervous system cell-containing spheroid; and a method for evaluating a test substance, the method including incubating a nervous system cell-containing spheroid in the presence of a test substance, and evaluating an effect of the test substance on the nervous system cell-containing spheroid, in which the nervous system cell-containing spheroid includes at least one kind of nerve cells and nervous system cells other than the nerve cells, and the proportion of the volume of one cell layer positioned at an outer edge of the spheroid to the volume of the entire spheroid is 15% to 30%.

What is provided is an ALS model cell that can be conveniently produced and is associated with a high proportion of cells in which a disease condition phenotype of ALS is reproduced. Disclosed are: a nerve cell having a causative gene of ALS incorporated into the genome of the nerve cell in an acquired manner; a co-culture product containing the nerve cell and an astrocyte having a causative gene of ALS incorporated into the genome of the astrocyte; a production method for ALS model cells, the production method including introducing a causative gene of ALS operably linked to a promoter for a eukaryotic cell, into a genome of nerve cells or into a genome of a co-culture product of nerve cells and astrocytes; and a screening method for a prophylactic or therapeutic drug for ALS, the screening method including: culturing ALS model cells in presence of a test substance; and evaluating a phenotype of the ALS model cells, in which the phenotype of the ALS model cells being closer to a wild-type phenotype as compared with a phenotype in absence of the test substance, implies that the test substance is a prophylactic or therapeutic drug for ALS.

Described herein is a microphysiological system for models of disease. Specifically, induced pluripotent stem cells (iPSCs) and iPSC-derived cells, including those obtained from disease patients, are seeded onto microfluidic chip devices to study cellular development and disease pathogenesis. Herein, neurodegenerative disease modeling, including Parkinson's Disease (PD) is shown to reproduce key PD pathology in a vascularized human model that contains neurons relating to PD pathology. Such compositions and methods are used for research for PD biomarkers, patient screening for PD risk assessment, and therapeutic discovery and testing. A panel of biomarkers are generated through analysis of living PD-chips by neural activity, whole transcriptomic, proteomic, and metabolomic analysis, and functional enzyme tests of media and tissue. Introducing therapeutics through a vasculature channel, coupled with blood brain barrier penetration studies can be assessed for efficacy in the human neural cells present in the PD-Chip.