The invention disclosed herein generally relates to methods and systems for converting stem cells into specific tissue(s) or organ(s) through directed differentiation. In particular, the invention disclosed herein relates to methods and systems for promoting human self-organizing single-rosette spheroids (SOSRS), a type of brain organoid, comprising neuroepithelium having either a dorsal cell fate or a ventral cell fate formation from pluripotent stem cells.

Provided are cortical interneurons and other neuronal cells and in vitro methods for producing such cortical interneurons and other neuronal cells by the directed differentiation of stem cells and neuronal progenitor cells. The present disclosure relates to novel methods of in vitro differentiation of stem cells and neural progenitor cells to produce several type neuronal cells and their precursor cells, including cortical interneurons, hypothalamic neurons and pre-optic cholinergic neurons. The present disclose describes the derivation of these cells via inhibiting SMAD and Wnt signaling pathways and activating SHH signaling pathway. The present disclosure relates to the novel discovery that the timing and duration of SHH activation can be harnessed to direct controlled differentiation of neural progenitor cells into either cortical interneurons, hypothalamic neurons or pre-optic cholinergic neurons. The present disclosure also relates to compositions of cortical interneurons, hypothalamic neurons or pre-optic cholinergic neurons, and their precursors, that are highly enriched and can be used in variety of application. These cells can be used therapeutically to treat neurodegenerative and neuropsychiatric disorders, and can be used for disease modeling and drug screening.

An object of the present invention is to provide a novel method that enables determination or evaluation of the undifferentiated state of human pluripotent stem cells simply, efficiently and non-invasively. The present invention provides a method for determining or evaluating the undifferentiated state of human pluripotent stem cells, comprising a step of detecting or measuring fibronectin in a culture supernatant of human pluripotent stem cells.

Provided are age-modified cells and method for making age modified cells by reducing or increasing the level of genomic nucleic acid methylation in the cells. The aging and/or maturation process can be accelerated or reduced and controlled for young, aged, mature and/or immature cells, such as a somatic cell, a stem cell, a stem cell-derived somatic cell, including an induced pluripotent stem cell-derived cell, by reducing or increasing the level of genomic nucleic acid methylation in the cells. Methods described by the present disclosure can produce age-appropriate cells from a somatic cell or a stem cell, such as an old cell, young cell, immature cell, and/or a mature cell. Such age-modified cells constitute model systems for the study of late-onset diseases and/or disorders.

A method for characterizing stem cell differentiation includes harvesting differentiation media supernatant containing secreted analytes from key time points during a stem cell differentiation, performing at least one of a qualitative and a quantitative analysis of the differentiation media supernatant with respect to at least one secreted analyte, and identifying trends in analyte expression based on at least one of the qualitative and quantitative analysis of the differentiation media supernatant.

The methods and kits described herein are based, in part, to the discovery of a phenotype representing a fully-reprogrammed iPS cell and several reprogramming intermediates. The methods and kits described herein permit identification of fully-reprogrammed iPS cells and further permits one of skill in the art to monitor the emergence of iPS cells during the reprogramming process. The methods/kits can also be performed using real time using live cell imaging. Also described herein are methods for screening candidate reprogramming agents by monitoring the emergence of fully-reprogrammed iPS cells in the presence and absence of such an agent.

The disclosure provides nonsteroidal anti-inflammatory compositions and methods of use thereof. Specifically, the disclosure provides cell-free or substantially cell-free regenerative nonsteroidal anti-inflammatory compositions derived from placenta and/or from MSC cells isolated therefrom, methods for producing said compositions, and uses thereof to treat chronic and acute inflammatory conditions and diseases.

Measurements in test tissue and drug-treated tissue can be used to determine an effect of the drug, e.g., on cardiomyocytes. Optical measurements of test tissue (e.g., including immature or animal CMs) can be complemented with observations of the extracellular potential, e.g., using multi electrode arrays (MEAs), as part of accurately estimating the current density of an ion channel, e.g., the sodium channels. The estimating of an ion current density (e.g., by inversion) of the ion (e.g., sodium) current can also use an observation of the conduction velocity, which can be computed using measurements of extracellular waves across electrodes. Example optical measurements can be of a transmembrane voltage (Vm) and intracellular calcium concentration (Cai). An example electrical measurement can be of an extracellular potential (U).

The present invention is in the field of oncology, and more particularly of cancer stem cells. It relates to a method for producing cancer stem cells based on overexpression of Δ133ρ536 isoform, Δ133ρ53γ isoform, or both Δ133ρ536 and Δ133ρ53γ isoforms; a method for predicting the risk that treatment with a chemotherapeutic anti-cancer agent induces cancer stem cells in a subject suffering from cancer from a cancer sample of said subject, based on detection of an increase in Δ133ρ536 isoform, Δ133ρ53γ isoform, or both Δ133ρ536 and Δ133ρ53γ isoforms following chemotherapeutic anti-cancer treatment; to therapeutic uses of a combination of chemotherapeutic anti-cancer agent and an agent reducing Δ133p536 isoform, Δ133ρ53γ isoform, or both Δ133ρ536 and Δ133ρ53γ isoforms expression; and also to screening methods for anti-cancer stem cells agents.

The invention provides a method for mobilising haematopoietic stem and progenitor cells (HSPC) and/or mesenchymal stem cells (MSC) in a subject, the method comprising administering a selective beta-3 adrenergic receptor (AR) agonist and an inhibitor of the CXCR4/CXCL12 chemokine axis to the subject.