The present disclosure relates generally to methods of inducing differentiation of pluripotent stem cells into enteric nitrergic neurons, and enteric nitrergic neurons produced by such methods. Also provided are used of such enteric nitrergic neurons for screening potential therapeutic agents suitable for preventing and/or treating enteric nervous system disorders, such as gastroparesis, esophageal achalasia, chronic intestinal pseudo-obstruction, and hypertrophic pyloric stenosis, and applications of such enteric nitrergic neurons in regenerative medicine, such as cell transplantation therapy, for preventing and/or treating enteric nervous system disorders.

The present invention relates to, inter alia, an engineered cell (e.g., iPSC, IPS-derived NK, or NK cell) comprising a disrupted B2M gene and an inserted polynucleotide encoding one or more of SERPINB9, a fusion of IL15 and IL15Rα, and/or HLA-E. The engineered cell can further comprise a disrupted CIITA gene and an inserted polynucleotide encoding a CAR, wherein the CAR can be an anti-BCMA CAR or an anti-CD30 CAR. The engineered cell may further comprise a disrupted ADAM17 gene, a disrupted FAS gene, a disrupted CISH gene, and/or a disrupted REGNASE-1 gene. Methods for producing the engineered cells are also provided, and therapeutic uses of the engineered cells are also described. Guide RNA sequences targeting described target sequences are also described.

The present invention provides a method for producing a retinal progenitor cell, including (1) a first step of subjecting pluripotent stem cells to floating culture in a serum-free medium to form an aggregate of pluripotent stem cells, and (2) a second step of subjecting the aggregate formed in step (1) to floating culture in a serum-free medium or serum-containing medium each being free of a substance acting on the Sonic hedgehog signal transduction pathway but containing a substance acting on the BMP signal transduction pathway, thereby obtaining an aggregate containing retinal progenitor cells.

The present invention provides a method for producing dopaminergic neuron progenitor cells from pluripotent stem cells, which method comprises the steps of: (i) performing adherent culture of pluripotent stem cells on an extracellular matrix in a medium containing a reagent(s) selected from the group consisting of BMP inhibitor, TGFβ inhibitor, SHH signal-stimulating agent, FGF8, and GSK3β inhibitor; (ii) collecting Corin- and/or Lrtm1-positive cells from the cells obtained in Step (i) using a substance which binds to Corin and/or a substance which binds to Lrtm1; and (iii) performing suspension culture of the cells obtained in Step (ii) in a medium containing a neurotrophic factor.

An object of the present invention is to provide a method of producing an intestinal epithelial cell, which has a large number of cells per area and a high accuracy of kinetic prediction for a CYP3A4 substrate drug such as midazolam, by inducing the differentiation of a pluripotent stem cell, as well as the intestinal epithelial cell, a cell sheet, an evaluation method for a test substance, a screening kit for a test substance, and a cell preparation. According to the present invention, there is provided a production method for an intestinal epithelial cell, including a first differentiation step of differentiating a pluripotent stem cell into an intestinal stem cell, a proliferation step of proliferating the intestinal stem cell obtained in the differentiation step, and a second differentiation step of differentiating the intestinal stem cell obtained in the proliferation step into an intestinal epithelial cell, in which the proliferation step is a step of bringing the intestinal stem cell into a specific state.

The application provides biocompatible carriers comprising bone forming and/or cartilage forming cells and methods for making them. The application further provides pharmaceutical compositions comprising said ATMPs and method of treatments using said ATMPs. The application further relates to said ATMPS for use in the treatment of bone disorders, cartilage disorders and joint disorders. The current invention further relates to method of treatments of bone disorders, cartilage disorders and joint disorders.

A hydrogel capsule comprising a stem cell core that has been induced to differentiate into a hematopoietic lineage cell, and methods for the production of hematopoietic lineage cells from stem cells encapsulated in a hydrogel.

The invention provides culture platforms, cell media, and methods of differentiating pluriptent cells into hematopoietic cells. The invention further provides pluripotent stem cell-derived hematopoietic cells generated using the culture platforms and methods disclosed herein, which enable feed-free, monolayer culturing and in the absence of EB formation. Specifically, pluripotent stem cell-derived hematopoietic cell of this invention include, and not limited to, iHSC, definitive hemogenic endothelium, hematopoietic multipotent progenitors, T cell progenitors, NK cell progenitors, T cells, and NK cells.

The present invention relates to a composition for the differentiation of dental pulp stem cells into odontoblasts and an IgG or IgM type monoclonal antibody that specifically binds to the surface of odontoblasts differentiated from the stem cells. According to the present invention, BMP2 and BMP4 are optimally combined to significantly increase the differentiation efficiency of dental pulp stem cells into odontoblasts, to induce the mineralization of the matrix, and to improve the differentiation ability of odontoblasts into dentin. Further, the IgG or IgM monoclonal antibody that specifically binds to the surface of odontoblasts of the present invention is used to effectively isolate and purify odontoblasts, which can be useful for tissue regeneration and differentiation.

A method is provided for producing a live cartilaginous material useful for implantation into a patient. A method of treating a patient comprising implanting a cartilaginous material prepared according to the provided method in an anatomical site in a patient also is provided.