45 results about "Lineage specific" patented technology

Well-defined, xeno-free culture media which comprise a TGF-beta isoform or the chimera formed between IL6 and the soluble IL6 receptor (IL6RIL6), which are capable of maintaining stem cells, and particularly, human embryonic stem cells, in an undifferentiated state are provided. Also provided are cell cultures comprising the culture media and the stem cells and methods of expanding and deriving embryonic stem cells in such well-defined, xeno-free culture media. In addition, the present invention provides methods of differentiating ESCs or EBs formed therefrom for the generation of lineage specific cells.

The invention provides biomarker profiles of cellular metabolites and methods for screening chemical compounds including pharmaceutical agents, lead and candidate drug compounds and other chemicals using human embryonic stem cells (hESC) or lineage-specific cells produced therefrom. The inventive methods are useful for testing toxicity, particularly developmental toxicity and detecting teratogenic effects of such chemical compounds.

The present invention provides methods, improved cell culture medium and kits for promoting hematopoietic and mesenchymal stem and lineage-specific cell proliferation and differentiation by growth in the presence of angiotensinogen, angiotensin I (Al), AI analogues, AI fragments and analogues thereof, angiotensin II (AII), AII analogues, AII fragments or analogues thereof or AII AT₂ type 2 receptor agonists, either alone or in combination with other growth factors and cytokines.

The present invention relates to the field of stem cell biology, in particular the lineage specific differentiation of pluripotent or multipotent stem cells, which can include, but is not limited to, human embryonic stem cells (hESC) in addition to nonembryonic human induced pluripotent stem cells (hiPSC), somatic stem cells, stem cells from patients with a disease, or any other cell capable of lineage specific differentiation. Specifically described are methods to direct the lineage specific differentiation of hESC and/or hiPSC into floor plate midbrain progenitor cells and then further into large populations of midbrain fate FOXA2+LMX1A+TH+ dopamine (DA) neurons using novel culture conditions. The midbrain fate FOXA2+LMX1A+TH+ dopamine (DA) neurons made using the methods of the present invention are further contemplated for various uses including, but not limited to, use in in vitro drug discovery assays, neurology research, and as a therapeutic to reverse disease of, or damage to, a lack of dopamine neurons in a patient. Further, compositions and methods are provided for differentiating midbrain fate FOXA2+LMX1A+TH+ dopamine (DA) neurons from human pluripotent stem cells for use in disease modeling, in particular Parkinson's disease. Additionally, authentic DA neurons are enriched for markers, such as CD142, and A9 type neuronal cells.

Methods for making human ES cells and human differentiated cells and tissues for transplantation are described, whereby the cells and tissues are created following somatic cell nuclear transfer. The nuclear transfer donor is genetically modified prior to nuclear transfer such that cells of at least one developmental lineage are de-differentiated, i.e., unable to develop, thereby resolving the ethical dilemmas involved in reprogramming somatic cells back to the embryonic stage. The method concomitantly directs differentiation such that the desired cells and tissues may be more readily isolated.

Animal cells, notably adult fibroblasts, are advantageously reprogrammed in direct lineage reprogramming methods using defined factors to produce proliferative and multipotent induced cardiac progenitor cells (iCPC). The iCPC thus produced can be differentiated under suitable differentiation conditions to cardiac lineage cells including cardiomyocytes, smooth muscle cells, and endothelial cells, as evidenced by expression of lineage specific markers. Sets of factors effective in combination to reprogram the fibroblasts can include a set that includes some or all of 5 factors (Mesp1, Baf60c, Nkx2.5, Gata4, Tbx5), a set that includes some or all of 11 factors (Mesp1, Mesp2, Gata4, Gata6, Baf60c, SRF, Isl1, Nkx2.5, Irx4, Tbx5, Tbx20), a set that includes some or all of 18 factors (T, Mesp1, Mesp2, Tbx5, Tbx20, Isl1, Gata4, Gata6, Irx4, Nkx2.5, Hand1, Hand2, Tbx20, Tbx18, Tip60, Baf60c, SRF, Hey2), and a set that includes some or all of 22 factors (T, Mesp1, Mesp2, Tbx5, Tbx20, Isl1, Gata4, Gata6, Irx4, Nkx2.5, Hand1, Hand2, Tbx20, Tbx18, Tip60, Baf60c, SRF, Hey2, Oct4, Klf4, Sox2, L-myc).

A method of qualifying a mesenchymal stem cell (MSC) population is disclosed. The method comprises:

• • (a) ex vivo differentiating a population of mesenchymal stem cells originating from the subject towards a first lineage-specific cell, the first lineage-specific cell being associated with a brain disease;
  • (b) ex vivo differentiating a population of mesenchymal stem cells originating from a healthy subject towards the first lineage-specific cell;
  • (c) comparing an effect of the first lineage specific cell derived from the subject with an effect of the first lineage specific cell derived from the healthy subject on a second lineage specific cell associated with the brain disease, wherein a difference in the effect above or below a predetermined level is indicative of a qualification of a mesenchymal stem cell population for cell therapy of said brain disease.

Disclosed herein are methods of administering an agent targeting a lineage-specific cell-surface antigen and a population of hematopoietic cells that are deficient in the lineage-specific cell-surface antigen for immunotherapy of hematological malignancies.

he present invention is of a method of dynamically generating human embryoid bodies which can be used for generating lineage specific cells and cell lines. Specifically, the present invention can be used to generate ESC-differentiated cells for cell-replacement therapy.

Disclosed herein are compositions, methods, and kits for use in treating hematopoietic malignancies, the compositions, methods, and kits comprise a cytotoxic agent targeting cells expressing a lineage-specific cell-surface protein and a population of hematopoietic cells that express the lineage-specific cell-surface protein, the hematopoietic cells being manipulated such that they do not bind the cytotoxic agent.

The present disclosure provides a method of directly converting a stem cell into a lineage specific cell, comprising the steps of a) transfecting a stem cell with at least one expression vector comprising i) one or more cell lineage reprogramming factors operably linked to an inducible promoter and ii) a selection marker; and b) inducing the transfected stem cell from stem a) with an inducing agent to directly convert said stem cell into a lineage-specific cell. Particularly exemplified are methods of transfecting a stem cell with SA-ASCL1 (phospho-mutant), DLX2, LHX6 and miR-9/9*-124 linked to a doxycycline inducible promoter to convert the stem cell into an inhibitory neuron and transfecting with NeuroD2 linked to a doxycycline inducible promoter to convert a stem cell into an excitatory neuron. Methods of screening one or more factors and/or one or more genetic mutations that modulate a pre-selected activity of the lineage specific cell, kits and directly convertible stem cells obtained using method of the invention are also provided.

Disclosed herein are methods of administering an agent targeting a lineage-specific cell-surface antigen, e.g., CD33, and a population of hematopoietic cells that are deficient in the lineage-specific cell-surface antigen, e.g., CD33 for immunotherapy of hematological malignancies. Cells comprising mutations in CD33 are also provided, as are gRNAs targeting CD33.

Human pluripotent stem cells (hPSCs) have dual value as microphysiological laboratory models and regenerative therapeutics. hPSCs are epithelial cells, but the extent to which hPSCs and descendant epithelia can reconstitute lineage-specific functions remains poorly understood. Here the Inventors show that hPSCs in three-dimensional cultures and their differentiated descendants can functionally recapitulate tissue-specific epithelial morphogenesis, physiology, and disease.

A DNA construct containing an erythroid lineage-specific promoter operably linked to a nucleotide coding sequence of interest and a method of using the same in the prevention or treatment of a hematopoietic disorder such as a hemoglobinopathy are described. Further disclosed are erythroid-specific promoters and erythroid-specific enhancers that can be used in the DNA construct.