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.

A method of qualifying whether a cell population is a suitable therapeutic for treating an eye condition is disclosed. The method comprises analyzing co-expression of premelanosome protein (PMEL17) and at least one polypeptide selected from the group consisting of cellular retinaldehyde binding protein (CRALBP), lecithin retinol acyltransferase (LRAT) and sex determining region Y-box 9 (SOX 9) in the population of cells.

The present invention provides methods to promote the differentiation of pluripotent stem cells. In particular, the present invention provides an improved method for the formation of pancreatic endoderm, pancreatic hormone expressing cells and pancreatic hormone secreting cells. The present invention also provides methods to promote the differentiation of pluripotent stem cells without the use of a feeder cell layer.

This document relates to bioengineering and involves bioengineered thymus organoids and related humanized animal models. The thymus organoids and animal models have various commercial and clinical uses, including generating humanized antibodies, making antigen-specific human T cells, inducing transplantation tolerance, rejuvenating thymus functions, and modeling human diseases.

Provided are methods for producing population of cells enriched for cells exhibiting sinoatrial node like characteristics. The cells can be produced from human pluripotent cells. Also provided are methods for using the SAN-like cells for identifying agents that can mitigate drug-induced cardiac toxicity. Also provided is a method for mitigating drug induced cardiotoxicity comprising administering to a subject an effective amount of physcion or a derivative thereof.

Provided are methods for inducing differentiation of pluripotent stem cells, e.g., induced pluripotent stem cells, to form definitive endoderm. Also provided are methods for producing more committed endodermal cells such as hepatoblasts or hepatocytes.

A medium composition, containing a basic fibroblast growth factor (bFGF) at not less than 150 ng/mL is useful for culturing cells.

Methods for generating human committed midbrain neural stem cells (NSCs) and midbrain neural progenitor cells (midbrain NPCs) from human pluripotent stem cells are provided using chemically-defined culture media that allow for generation of the midbrain NPCs in as little as six days. The midbrain NPCs can be further differentiated to mature dopaminergic neurons. Culture media, isolated cell populations and kits are also provided.

A method of obtaining a pluripotent-like multipotent cell, including providing a cell of a first type which is not a pluripotent-like multipotent cell; contacting the cell of a first type with an agent capable of remodeling the chromatin and/or DNA of the cell; transiently increasing expression of at least one pluripotent gene regulator in the cell of a first type, to a level at which the at least one pluripotent gene regulator is capable of driving transformation of the cell of a first type into the pluripotent-like multipotent cell; and placing or maintaining the cell in a differentiation medium and maintaining intracellular levels of the at least one pluripotent gene regulator for a sufficient period of time to allow a stable pluripotent-like multipotent cell to be obtained; wherein the pluripotent-like multipotent cell so obtained does not exhibit teratoma formation in vivo.

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.