Immune effector cells and immune effector cell lines are modified to have increased resistance to TRAIL-induced cell death, by knockout of a TRAIL receptor or by linking a TRAIL receptor to an immune effector cell co-stimulatory domain, or both.

Abstract: We describe a robust human adult distal lung organoid method with a procedure for everting organoids to essentially turn them inside out. This then relocates the apical ACE2-expressing surfaces of cells to the organoid exterior, where they can then be easily infected by SARS-CoV-2 added to the tissue culture medium. Further, this method can be used for infection of any distal lung pathogen that infects apically. Alternatively, if a pathogen interacts basolaterally then eversion is not necessary, and the human adult distal lung organoids can be infected as is.

It is a subject to provide a means of preparing highly pure vascular endothelial progenitor cells in a simple and low-cost manner. It is also a subject to provide a method for efficiently proliferating vascular endothelial progenitor cells. High-purity vascular endothelial progenitor cells are prepared by the process of differentiating pluripotent stem cells into vascular endothelial progenitor cells and purifying the vascular endothelial progenitor cells using a difference in adhesion ability between the vascular endothelial progenitor cells constituting the cell population obtained in the process and other cells. On the other hand, vascular endothelial progenitor cells are cultured and expanded in the presence of a ROCK inhibitor, a GSK-3β inhibitor, and a TGF-β receptor inhibitor in addition to basic fibroblast growth factor and epidermal growth factor.

The current disclosure provides for methods of promoting differentiation of pluripotent stem cells into thymic epithelial cells or thymic epithelial cell progenitors as well as the cells obtained from the methods, and solutions, compositions, and pharmaceutical compositions comprising such cells. The current disclosure also provides for methods of using the thymic epithelial cells or thymic epithelial cell progenitors for treatment and prevention of disease, generating organs, as well as other uses, and kits.

Provided is a method for inducing differentiation of neural crest cells into neurons of the autonomic nervous system, the method including the step of culturing neural crest cells in the presence of at least one of a BMP signaling pathway activator, an SHH signaling pathway inhibitor, and a Wnt signaling pathway inhibitor.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near at least one gene that encodes a survival factor, wherein the genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor.

An object of the present invention is to provide a method of efficiently producing a maturated megakaryocytic cell line from hematopoietic progenitor cells. The present invention provides a method for producing megakaryocytes from hematopoietic progenitor cells, comprising (i) forcibly expressing an apoptosis suppression gene and an oncogene in hematopoietic progenitor cells and culturing the cells, and (ii) arresting forced expression of the apoptosis suppression gene and the oncogene and culturing the hematopoietic progenitor cells.

Provided herein are populations of IL2 Dependent haNK® cells, which express a high affinity CD16 but does not express IL-2. These cells maintain stable expression of Fc receptor CD16 while retaining cytotoxicity. In some embodiments, the expression level of CD16 decreases no more than 20% when the cells are activated as compared to expression level of CD16 on the cells before activation. Compositions and kits comprising the cells, and methods of making and using the IL2 Dependent haNK® cells are also provided.

An object of the present invention is to provide a method for producing T cells or NK cells, a culture medium for culturing T cells or NK cells, a method for culturing T cells or NK cells, a method for maintaining the undifferentiated state of undifferentiated T cells, and a growth promoter for T cells or NK cells, which are capable of efficiently proliferating T cells or NK cells and maintaining the state of the cells (for example, undifferentiated property).

The present invention relates to a method for producing T cells or NK cells including culturing T cells or NK cells in a culture medium containing a bisbenzylisoquinoline alkaloid represented by formula (X-1) or formula (X-2) or a compound resulting from cleavage of one ether bond thereof or a pharmaceutically acceptable salt thereof, and the like.

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Featured are cells and methods of use thereof for modulating an antigen-specific immune response in a subject. The cells comprise a set of transgenes comprising two or more of PD-L1, HLA-G or H2-M3, Cd47, Cd200, FASG or FasL, Ccl21 or Ccl21b, MfgeS and Serpin B9 or Spi6, that shield the cells from immune surveillance (ie. “cloaking genes”). The cells can be used to induce immune tolerance to an antigen (e.g., a donor alloantigen or a self-antigen), or to induce an immune response to (e.g., induce the production of antibodies directed against) a non-self antigen.