10 results about "Erythroblast" patented technology

The present disclosure provides, in various aspects and embodiments, methods for generating hematopoietic lineages for cell therapy, including erythroid progenitor cells, progenitor cell erythroblasts, granulocyte-macrophage progenitor cells (GMP), and megakaryocyte erythroid progenitor cells (MEPs) and erythroid cells. In various embodiments, the invention provides efficient in vitro methods for developing such hematopoietic lineages, including but not limited to progenitor erythroblasts and erythroblasts lineages, from human induced pluripotent stem cells (iPSCs). The cells produced in various embodiments according to the present disclosure are functional and / or more closely similar to corresponding lineages isolated from peripheral blood or bone marrow. The invention also provides isolated cells and cell compositions produced by the methods disclosed herein, as well as methods for cell therapy.

Novel methods for producing self-renewing erythroblasts (SREs) from induced pluripotent stem cells (iPSCs) or CD34+ cells are provided. Also provided are genetically modified iPSCs or CD34+ cells having a constitutively active stem cell factor (SCF) receptor and a constitutively active Janus kinase 2 (JAK2) that can differentiate into enucleated red blood cells, self-renew, and expand in culture media for an extended period of time. In particular, the disclosed methods completely eliminate the need for SCF and Epo.

To provide a therapeutic agent enabling treatment of a malignant tumor.SOLUTION: A therapeutic agent comprising a substance that recognizes a target expressed in an erythroblast, where the therapeutic agent is administered such that, during a dosing period, a serum concentration of the substance in a subject administered with the therapeutic agent is maintained at 10% or more of a maximum value after administration.SELECTED DRAWING: None

The present invention provides the use of ATR / Chk1 signaling pathway inhibitors in promoting enucleation of red blood cells, and experiments prove that ATR / Chk1 signaling pathway inhibitors can promote enucleation in the in vitro differentiation system of erythroid cells derived from fetal liver and the in vitro differentiation system of erythroid cells derived from peripheral blood, and can promote enucleation of erythroblasts in bone marrow. ATR / Chk1 signaling pathway inhibitors can also promote enucleation of erythroblasts in the bone marrow and spleen of thalassemia subjects, and have good application prospects in the treatment of diseases related to abnormal enucleation of red blood cells.

BCL11A plays a critical role in the regulation of hemoglobin production, specifically in the switch from fetal hemoglobin (HbF) to adult hemoglobin (HbA) during development. BCL11A represents a target to develop therapies for β-hemoglobinopathies by reactivating HbF. The inventors leading to a better yield for the proteomic analysis of histidine phosphorylations in a whole proteome. They identify a phosphorylation on histidine of BCL11A by immunoprecipitation of BCL11A and by the detection of its phosphorylations on histidines by Western blot. Furthermore, the knock down of NME1 and NME2 by CRISPR / Cas9 in HUDEP2 erythroid cell line induces the expression of fetal hemoglobin, suggesting that NME1 / 2 could be involved in fetal to adult globin switch probably through the regulation of histidine phosphorylation of BCL11A. HUDEP-2 cell line is still able to differentiate until the orthochromaic erythroblast stage and do not show any increase in cell death.

The present disclosure provides techniques for detecting blood disorders using cell-free DNA in a blood sample, e.g., using plasma or serum. For example, an analysis can target one or more differentially methylated regions specific to a particular blood cell lineage (e.g., erythroblasts). Methylation levels can be quantified from the analysis to determine the amount of methylated or unmethylated DNA fragments in the cell-free mixture of the blood sample. The methylation levels can be compared to one or more cutoff values, e.g., corresponding to a normal range for the particular blood cell lineage, as part of determining a level of a blood disorder.

Novel methods for producing self-renewing erythroblasts (SREs) from induced pluripotent stem cells (iPSCs) or CD34+ cells are provided. Also provided are genetically modified iPSCs or CD34+ cells having a constitutively active stem cell factor (SCF) receptor and a constitutively active Janus kinase 2 (JAK2) that can differentiate into enucleated red blood cells, self-renew, and expand in culture media for an extended period of time. In particular, the disclosed methods completely eliminate the need for SCF and Epo.

A method, just requiring simple pretreatment, of concentration measurement for reticulocytes or nucleated erythrocytes includes a staining step, a removal step, and a measurement step. In the staining step, reticulocytes or nucleated erythrocytes among red blood cells contained in a blood specimen are stained. In the removal step, the blood specimen is mixed with a surfactant to extract hemoglobin from the red blood cells. In the measurement step, using the blood specimen having undergone the staining step and the removal step, the concentration of the reticulocytes or nucleated erythrocytes contained in the blood specimen is measured.

The invention provides application of an ATR / Chk1 signal channel inhibitor in promoting erythrocyte denucleation, and experiments prove that the ATR / Chk1 signal channel inhibitor can promote denucleation of an erythroid in-vitro differentiation system derived from fetal liver and an erythroid in-vitro differentiation system derived from peripheral blood and promote denucleation of erythroblasts in bone marrow. The ATR / Chk1 signaling pathway inhibitor can also promote erythrocyte denucleation in bone marrow and spleen of a thalassemia subject, and has a good application prospect in treatment of erythrocyte denucleation abnormality related diseases.

The present disclosure, in various aspects and embodiments, provides methods for generating hematopoietic lineages for cell therapy, including erythroid progenitor cells, progenitor erythroblasts, granulocyte-macrophage progenitor cells (GMPs), and megakaryocyte erythroid progenitor cells (MEPs), and erythroid cells. In various embodiments, the invention provides for efficient ex vivo processes for developing such hematopoietic lineages, including but not limited to progenitor erythroblast cells and erythroblast cell lineages, from human induced pluripotent stem cells (iPSCs). Cells generated according to the disclosure in various embodiments are functional and / or more closely resemble the corresponding lineage isolated from peripheral blood or bone marrow. The present invention also provides isolated cells and cell compositions produced by the methods disclosed herein, as well as methods for cell therapy.