Hematopoeitic stem/progenitor cells (HSPC) and/or non-T effector cells are modified to express an extracellular component including a tag cassette. The tag cassette can be used to activate, promote proliferation of, detect, enrich, isolate, track, deplete and/or eliminate modified cells. The cells can also be modified to express a binding domain.

Method and compositions for inducing the self-renewal of stem/progenitor supporting cells comprised by a cochlear cell population, including inducing the stem/progenitor cells to proliferate while maintaining, in the daughter cells, the capacity to differentiate into hair cells.

Compositions and provided to induce cells of the inner ear to renter the cell cycle and to proliferate. In particular, hair cells are induced to proliferate by administration of a composition which activates the Myc and Notch. Supporting cells are induced to transdifferentiate to hair cells by inhibition of Myc and Notch activity or the activation of Atoh1. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.

The present disclosure provides methods for immortalizing precursor cells that are non-terminally differentiated cells such as stem cells, the methods comprising culturing the precursor cells in the presence of a Notch 1 agonist, Notch 2 agonist or Notch 1 agonist and Notch 2 agonist (and, in particular embodiments, one or more growth factors) that support the proliferation but not differentiation of the non-terminally differentiated cells. The present disclosure further provides methods to induce the differentiation of immortalized cells, comprising growing the cells in the presence of a Notch 1 agonist, Notch 2 agonist or Notch 1 agonist and Notch 2 agonist and at least one growth factor which supports the differentiation of the cell into a more specialized cell type. The immortalized and/or differentiated cells of the disclosure can be used to repopulate cell populations that have been diminished, for example as a result of infection or exposure to certain drugs. The disclosure further provides a cell culture comprising a population of non-terminally differentiated cells immortalized by the methods of the present disclosure and kits comprising reagents that promote the immortalization of precursor cells.

The present invention is a method of creating a population of hemogenic endothelial cells with arterial specification and enhanced T cell potential. In one embodiment, the method uses ETS transgene induction at the mesodermal stage of differentiation. In another embodiment, the method activates ERK and NOTCH signaling at the mesodermal stage of differentiation.

The invention relates to differentiation methods for progenitor cells, e.g. mammalian epithelial stem cells, differentiation media for use in said methods, organoids and cells obtainable by said methods and uses, including therapeutic uses, thereof.

The invention relates to a neural tissue unit for use in implantation into the nervous system of a human or non-human mammal, wherein said neural tissue unit contains differentiated post-mitotic neuronal cells in an extracellular matrix, said unit being obtained from a cellular microcompartment comprising a hydrogel capsule surrounding the neural tissue unit, and said hydrogel capsule being at least partially removed before use of the neural tissue unit. The invention also relates to a process for preparing such a neural tissue unit.

The present invention aims to increase cytotoxic activity of an immunocompetent cell to thereby enhance a therapeutic effect against diseases such as cancers, and provides an immunocompetent cell having decreased diacylglycerol kinase activity, which cell expresses a fusion protein including IL-15 and an IL-15 receptor α subunit, and which cell expresses a chimeric antigen receptor.

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.

The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods, and to uses of said organoids.