Provided herein are methods of generating a population of enucleated erythroid cells.

Provided is a method for genetically editing an enhancer locus of hematopoietic stem cell BCL11A, comprising: disrupting the CTTCCT region of a BCL11A genome by gene editing technology. The genetically edited hematopoietic stem cells have normal cell functions and can significantly increase the expression of fetal hemoglobin, thereby being used for the treatment of thalassemia and sickle cell anemia.

The present disclosure relates to the production of red blood cells from hematopoietic stem cells, by differentiating such cells in the presence of a protein that induces cell survival and proliferation.

Methods for generating enucleated erythroid cells using pluripotent stem cells are provided. The methods permit the production of large numbers of cells. The cells obtained by the methods disclosed may be used for a variety of research, clinical, and therapeutic applications. Methods for generating megakaryocyte and platelets are also provided.

The invention provides culture platforms, cell media, and methods of differentiating pluriptent cells into hematopoietic cells. The invention further provides pluripotent stem cell-derived hematopoietic cells generated using the culture platforms and methods disclosed herein, which enable feed-free, monolayer culturing and in the absence of EB formation. Specifically, pluripotent stem cell-derived hematopoietic cell of this invention include, and not limited to, iHSC, definitive hemogenic endothelium, hematopoietic multipotent progenitors, T cell progenitors, NK cell progenitors, T cells, and NK cells.

Methods and compositions of erythroid cells that produce adult -hemoglobin, generated by culturing CD31+, CD31+/CD34+ or CD34+ cells from embryonic stem cells under serum-free culture conditions.

Multi-step methods for the in vitro production of enucleated red blood cells and the enucleated red blood cells thus prepared are provided. Such enucleated red blood cells may express fusion proteins comprising an antigen binding protein which allows the red blood cell to bind a toxin or an antigen of a pathogen. Also described herein are methods for neutralizing a toxin or pathogen in a subject by administering enucleated red blood cells that express any of the fusion proteins provided herein.

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 and expanding human hemangio-colony forming cells and non-engrafting hemangio 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, non-engrafting hemangio 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. Human non-engrafting hemangio cells are a novel progenitor cell population that is related to but distinct from the hemangioblast and human hemangio-colony forming cells. The invention also provides compositions, preparations, and solutions comprising hemangio-colony forming cells, non-engrafting hemangio cells or cells differentiated therefrom. The compositions, preparations, and solutions include cryopreserved preparations and substantially purified preparations, as well as mixed compositions formulated in combination with related hemangioblast progenitor cell types that can engraft into the bone marrow.

This disclosure relates a composition and method for promoting the reprogramming of somatic cells to induced pluripotent stem cells, the composition comprising gelatin and laminin. The disclosure further relates to a method of preparing somatic cells for producing induced pluripotent stem cells and a method for producing induced pluripotent stem cells, and thus provides method useful for the production of expanded somatic cells and induced pluripotent stem cells for use in research and therapy. Thus, the disclosure provides a method of preparing somatic cells for producing induced pluripotent stem cells, the method comprising: (i) isolating somatic cells from a sample, and (ii) expanding the somatic cells for a predetermined period of time, wherein the expanded somatic cells express TERT1, as well as a method for producing induced pluripotent stem cells from said expanded somatic cells by (a) introducing genetic elements, optionally episomal genetic elements, that express induced pluripotent stem cells reprogramming factors into said expanded somatic cells and (b) culturing said expanded somatic cells comprising the genetic elements, thereby producing induced pluripotent stem cells.