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.

Methods of generating and expanding human hemangio-colony forming cells in vitro and methods of expanding and using such cells are disclosed. The methods permit the production of large numbers of hemangio-colony forming cells as well as derivative cells, such as hematopoietic and endothelial cells. The cells obtained by the methods disclosed may be used for a variety of research, clinical, and therapeutic applications.

Materials and methods for treating a patient with a hemoglobinopathy, both ex vivo and in vivo, and materials and methods for creating permanent changes to the genome that can result in at least one deletion, insertion, modulation, or inactivation of a transcriptional control sequence of a BCL11A gene in a cell by genome editing.

The present invention provides a pharmaceutical composition for treating chronic stroke, involving injection via brain into the cranium of a patient having chronic stroke for six months or more; the pharmaceutical composition is a suspension at least comprising TS stem cells, an active synergistic component and a growth factor, wherein the expression level of CD34 and CD45 of the TS stem cells is 10% or less, and the expression level of CD90 and CD105 is 90% or more; the active synergistic component is an extracellular vesicle; the growth factor is at least one selected from the group consisting of HGF, G-CSF, Fractalkine, IP-10, EGF, IL-1α, IL-1β, IL-4, IL-5, IL-13, IFNγ, TGFα and sCD40L. The present invention overcomes the limitations of previous cell therapy and provides a cell-based preparation that is clinically safe and therapeutically effective for chronic cerebral stroke.

The disclosure features methods of correcting a mutation in the human beta-globin (HBB) gene in a cell or population of cells. The disclosure also features methods of increasing repair of a DNA double stranded break (DSB) in an HBB gene by the homology-directed repair (HDR) pathway. The disclosure also features compositions for use in the methods.

Provided herein are compositions and methods for improving the genome-wide specificities of targeted base editing technologies.

Provided are small molecule inhibitors for amplifying hematopoietic stem cells (HSCs) and a combination thereof. The small molecule inhibitors and the combination thereof can maintain the sternness of hematopoietic stem cells while promoting the in vitro amplification of hematopoietic stem cells (HSCs).

A method of producing helper T cells, comprising: (i) culturing T cells, which have been induced from pluripotent stem cells and into which a CD4 gene or a gene product thereof has been introduced, in a medium containing IL-2 and IL-15; and (ii) isolating CD40L-highly expressing T cells from cells obtained in step (i).

Embodiments herein relate to in vitro production methods of hematopoietic stem cell (HSC) and hematopoietic stem and progenitor cell (HSPC) that have long-term multilineage hematopoiesis potentials upon in vivo engraftment. The HSC and HSPCs are derived from pluripotent stem cells-derived hemogenic endothelia cells (HE) by non-integrative episomal vectors-based gene transfer.

A method to expand hematopoietic stem and progenitor cells (HSPC) wherein the method comprises obtaining an isolated population of HSPC the culturing the isolated population of HSPC in the presence of a histone deacetylase inhibitor (HDAC inhibitor), to form a cultured population, then adding an aminothiol compound to the cultured population.