According to the invention fibroblast-like cells obtained from heart muscle biopsies, which are CD90 negative, CD105 positive, CD117 negative and/or CD166 positive as well as cell preparations of such cells for therapy of heart diseases as well as a method for providing the latter are disclosed. The cells according to the invention are characterized by a good cultivability in cell culture. Furthermore a method for obtaining the cells and cell preparations according to the invention are disclosed.

A method of obtaining a neural multipotent, unipotent or somatic cell, including: i) providing a cell of a first type which is not a neural multipotent, unipotent or somatic cell; ii) increasing expression of at least one neural multipotent or unipotent gene regulator in the cell of a first type, to a level at which the at least one neural multipotent or unipotent gene regulator is capable of driving transformation of the cell of a first type into the neural multipotent, unipotent or somatic cell, wherein the at least one multipotent or unipotent gene regulator is Musashi1 (Msi1), Neurogenin 2 (Ngn2), or both Msi1 and Ngn2; and iii) placing or maintaining the cell in a neural cell culture medium and maintaining sufficient intracellular levels of the at least one multipotent or unipotent gene regulator for a sufficient period of time to allow a stable neural multipotent, unipotent or somatic cell to be obtained.

The present invention relates to the directed differentiation of mammalian pluripotent stem cells, especially human pluripotent stem (hPS) cells, into endodermal cells. In particular, the present invention relates to the treatment of mammalian pluripotent stem cells, especially hPS cells, with a DNA demethylating agent while undergoing differentiation into endodermal. The inventors have, as disclosed herein, found that exposing differentiating mammalian pluripotent stem cells, especially hPS cells, to a DNA demethylating agent leads to an improved morphology and improved yield of endodermal cells. The treatment with a DNA de-methylating agent also leads to a significant down-regulation of expression of the stem cell marker Oct4 and to an improved expression of endoderm specific markers, notably sox17, cxcr4 and hhex.

The present invention pertains to a method for the generation of neurotoxin-sensitive, neuronal differentiated cells comprising the steps of: a) cultivating tumor cells which are able to differentiate into neuronal cells in a culture medium under conditions and for a time which primes said tumor cells for neuronal differentiation; and b) cultivating the tumor cells primed for neuronal differentiation of a) in a differentiation medium having an osmolality of 100 to 270 mOsm/kg, and comprising (i) B27 supplement and/or (ii) N2 supplement, for at least 3 days, thereby obtaining neurotoxin-sensitive, neuronal differentiated cells. The invention further relates to neurotoxin-sensitive, neuronal differentiated cells obtainable by the method of the invention. In addition, the invention encompasses a method for determining the activity of a neurotoxin polypeptide comprising the steps of: a) contacting the neurotoxin-sensitive, neuronal differentiated cells obtainable by the method of the invention with a neurotoxin polypeptide; b) cultivating the neurotoxin-sensitive, neuronal differentiated cells of step a) for 3 to 74 hours or 72 hours under conditions which allow for the neurotoxin polypeptide to exert its biological activity; and c) determining the activity of the neurotoxin polypeptide in the said cells after cultivation according to step b). Finally, the invention provides for a medium comprising OptiMEM, FBS, B27 supplement, and N2 supplement.

The present invention relates to iPSC produced from fibroblast obtained from a subject affected by a neurodevelopmental disorder entailing intellectual disability (ID) and/or a disorder belonging to the Autism Spectrum Disorder (ASD) and/or Schizophrenia (SZ) and uses thereof. The present invention also relates to a cortical neural progenitor cell or a terminally differentiated cortical glutamatergic or gabaergic neuronal cell or a neural crest stem cell line, a mesenchymal stem cell line produced from the iPSC or iPSC line. The invention also relates to method for identifying a compound for the treatment and/or prevention of a neurodevelopmental disorder entailing intellectual disability (ID) and/or a disorder belonging to the Autism Spectrum Disorder (ASD) and/or Schizophrenia (SZ) and to a LSD1 inhibitor or a HDAC2 inhibitor for use in the treatment of such disorders.

The present invention relates to directed differentiation and maturation of mammalian hepatocytes, such as human hepatocytes. The hepatocyte obtained in accordance with the present invention show a phenotype which is more similar to that of primary hepatocytes than previously shown. In particular, the present invention relates to exposure of mammalian hepatocytes, such as human hepatocytes, to at least one maturation factor selected from the group consisting of Src kinase inhibitors, vitamin D including precursors, metabolites and analogs thereof, hypoxia inducing compounds, sphingosine and sphingosine derivatives, activators of peroxisome proliferator-activated receptors (PPARs), platelet-activating factor (PAF), PKC inhibitors, and combinations thereof.

Provided is a method including providing a population of cells including a target type of differentiated cells having a pre-identified cytoskeletal profile and at least one cell selected from undifferentiated cells, differentiating cells and differentiated cells being different from the target type of differentiated cells; and incubating the population of cells with a cytotoxic agent, in an amount and for a time period effective to form a modified population of cells including predominantly or consisting essentially of the target type of differentiated cells. The pre-identified cytoskeletal profile can include the presence of class III -tubulin on neuronal cells and the population of cells includes neural cells and neuronal cells.

The present disclosure provides method of processing neural cells comprising extracting one or more brain components from an animal, dissociating cells from the brain components to form a brain cell composition, purifying the neural cells from the brain cell composition, and culturing the neural cells. Further, the present disclosure provides in vitro assays and related kits utilizing the neural cells, for example in use to screen compounds or therapeutics for neurological diseases or disorders.

Objects of the present invention are to provide a method for directly obtaining pluripotent stern cells which do not have tumorigenic property from body tissue and the thus obtained pluripotent stem cells. The present invention relates to SSEA-3 (+) pluripotent stern cells that can be isolated from body tissue.

A novel family of human mitochondrial RNAs, referred to as chimeric RNAs, which are differentially expressed in normal, pre-cancer and cancer cells, are described. Oligonucleotides targeted to the chimeric RNAs are provided. The described oligonucleotides or their analogs can be used for cancer diagnostics and cancer therapy as well as for research. In one embodiment of this invention, these oligonucleotides hybridize with the sense or with the antisense mitochondrial chimeric RNAs, and the result of the hybridization is useful to differentiate between normal proliferating cells, pre-cancer cells and cancer cells. In another embodiment of the invention, the compositions comprise oligonucleotides that hybridize with the human chimeric RNAs resulting in cancer cell and pre-cancer cell death, while there is no effect in normal cells, constituting therefore, a novel approach for cancer therapy.