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.

Methods of generating spinal cord glutamatergic interneurons (V2a interneurons) from human pluripotent stem cells (hPSCs) are provided. A method of the present disclosure may include culturing a first population of hPSCs in vitro in a neural induction medium that includes: a retinoic acid signaling pathway activator; a sonic hedgehog (Shh) signaling pathway activator; and a Notch signaling pathway inhibitor, wherein the culturing results in generation of a second population of cultured cells containing CHX10+ V2a interneurons. Also provided are non-human animal models that include the hPSC-derived spinal cord glutamatergic interneurons, and methods of producing the non-human animal models.

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 for rejuvenating glial progenitor cells and rejuvenated glial progenitor cells rejuvenated by such method are disclosed. The method comprises introducing a population of genetically modified glial progenitor cells into the brain and/or brain stem of a subject, wherein the genetically modified glial progenitor cells have increased expression of one or more genes compared to the same type of glial progenitor cells that have not been genetically modified, and wherein the one or more genes are selected from the group consisting of ARX, CEBPZ, DLX1, DLX2, ELK1, ETS1, ETV4, KLF16, MYBL2, MYC, NFYB, POU3F1, SMAD1, SOX3, SP5, TCF12, TFDP1, TP53, ZIC3 and ZNF195.

Among the various aspects of the present disclosure is the provision of methods and compositions for the generation of functionally mature beta cells having enhanced SIX2+ activity and therapeutic benefit and uses thereof. An aspect of the present disclosure provides for a method of generating SIX2-enhanced SC-β cells. In some embodiments, the method comprises providing a population of SC-β cells (or EP cells); providing a SIX2 positive regulator; and/or incubating the population of SC-β cells and the SIX2 positive regulator.

Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. The derivative cells provided herein have stable and functional genome editing that delivers improved or enhanced therapeutic effects. Also provided are therapeutic compositions and the use thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors in combination therapies.

The present invention relates to a method for preparation of mesenchymal stem cells from human pluripotent stem cells and, more particularly, to a method for preparation of mesenchymal stem cells, wherein mesenchymal stem cells differentiated from embryoid bodies of a certain size in a xeno-free and serum-free environment are prepared, whereby the mesenchymal stem cells exhibit increased safety and maintain their own characteristics for a long period of time. A method for preparation of mesenchymal stem cells from human pluripotent stem cells according to the present invention employs a feeder cell-free, xeno-free, and serum-free culture environment to solve the problem of contamination with a foreign animal-derived material and allow the preparation of highly safe mesenchymal stem cells. In addition, the method utilizes spheroidal embryoid bodies to form mature embryoid bodies uniform in shape and size, thereby improving the differentiation efficiency to mesenchymal stem cells and exhibiting an exceptional effect of stably maintaining mesenchymal stem cell characteristics even after a long-term subculture, such as 20 or more passages, through which human pluripotent stem cell-derived mesenchymal stem cells can be prepared in a large amount. Therefore, the invention is advantageous for commercializing cell therapeutic agents superb in safety and efficiency.

The present invention relates to a gene therapy vector which is useful in the treatment or prevention of hypertrophic cardiomyopathy in a subject in need thereof. The gene therapy vector of the invention comprises a nucleic acid sequence encoding a cardiac sarcomeric protein and a cardiomyocyte-specific promoter which is operably linked to said nucleic acid sequence. The invention furthermore relates to a cell which comprises the gene therapy vector. Pharmaceutical compositions which comprise the gene therapy vector and/or a cell comprising said vector are also provided. In another aspect, the invention relates to a method for treating or preventing hypertrophic cardiomyopathy in a subject by introducing the gene therapy vector of the invention into a subject in need of treatment.

The invention relates to induced pluripotent stem cells that are generated from cells, for example Adult Stem Cells, that are conditionally-immortalisable. In particular, the invention relates to induced pluripotent stem cells generated from stem cell lines comprising a controllable transgene for conditional immortalisation, and the progeny of those induced pluripotent stem cells such as cells of the haematopoietic lineage. Induced pluripotent stem cells, haematopoietic progeny cells derived from those pluripotent cells, compositions comprising those cells, methods of making all of those cells, and uses of all of those cells are also described.

The present invention relates to a differentiation method for obtaining a large quantity of microglia by patterning, proliferating, culturing, and inducing the differentiation of yolk sac-mimic 3D organoids prepared from human pluripotent stem cells, wherein the microglia thus obtained in a large quantity exhibit significantly superior effects in terms of yield, purity, and storage stability compared to cells differentiated by existing differentiation methods, and thus may be utilized in research on lesions and therapeutic mechanisms of brain diseases, and drug screening platforms.