Abstract: The present invention relates to methods of isolating a purified or enriched population of cortical or striatal immature interneuron progenitor cells and the isolated purified or enriched population of immature interneuron progenitor cells. Methods of treating a condition mediated by a loss or deficiency of interneuron function using the purified or enriched population of immature interneuron progenitor cells are also disclosed.

Abstract: The present invention relates to the field of stem cell biology, in particular the linage specific differentiation of pluripotent or multipotent stem cells, which can include, but is not limited to, human embryonic stem cells (hESC), human induced pluripotent stem cells (hiPSC), somatic stem cells, cancer stem cells, or any other cell capable of lineage specific differentiation. Specifically described are methods to direct the lineage specific differentiation of hESC and/or hiPSC to nociceptors (i.e. nociceptor cells) using novel culture conditions. The nociceptors made using the methods of the present invention are further contemplated for various uses including, but limited to, use in in vitro drug discovery assays, pain research, and as a therapeutic to reverse disease of, or damage to, the peripheral nervous system (PNS). Further, compositions and methods are provided for producing melanocytes from human pluripotent stem cells for use in disease modeling.

Abstract: The present invention relates to the field of stem cell biology, in particular the linage specific differentiation of pluripotent or multipotent stem cells, which can include, but is not limited to, human embryonic stem cells (hESC), human induced pluripotent stem cells (hiPSC), somatic stem cells, cancer stem cells, or any other cell capable of lineage specific differentiation. Specifically described are methods to direct the lineage specific differentiation of hESC and/or hiPSC to nociceptors (i.e. nociceptor cells) using novel culture conditions. The nociceptors made using the methods of the present invention are further contemplated for various uses including, but limited to, use in in vitro drug discovery assays, pain research, and as a therapeutic to reverse disease of, or damage to, the peripheral nervous system (PNS). Further, compositions and methods are provided for producing melanocytes from human pluripotent stem cells for use in disease modeling.

Abstract: Provided are age-modified cells and method for making age modified cells using progerin or a progerin-like protein. The aging and/or maturation process can be accelerated and controlled for young 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 contacting with progerin or a progerin-like protein. Methods described by the present disclosure can produce age-appropriate cells from a somatic cell or a stem cell, such as an old cell and/or a mature cell. Such age-modified cells constitute model systems for the study of late-onset diseases and/or disorders.

Abstract: 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.

Abstract: GUCY2C receptor ligands conjugated to diagnostic and/or therapeutic moieties, methods of making such GUCY2C receptor ligands conjugates, and methods of using such GUCY2C receptor ligands conjugates, such as in the diagnosis and/or treatment of Parkinson's disease, are described.

Abstract: 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.

Abstract: The present invention relates generally to the field of cell biology of stem cells, more specifically the directed differentiation of pluripotent or multipotent stem cells, including human embryonic stem cells (hESC), somatic stem cells, and induced human pluripotent stem cells (hiPSC) using novel culture conditions. Specifically, methods are provided for obtaining neural tissue, floor plate cells, and placode including induction of neural plate development in hESCs for obtaining midbrain dopamine (DA) neurons, motorneurons, and sensory neurons. Further, neural plate tissue obtained using methods of the present inventions are contemplated for use in co-cultures with other tissues as inducers for shifting differentiation pathways, i.e. patterning.

Abstract: The present invention relates to the field of stem cell biology, in particular the linage specific differentiation of pluripotent or multipotent stem cells, which can include, but is not limited to, human embryonic stem cells (hESC), human induced pluripotent stem cells (hiPSC), somatic stem cells, cancer stem cells, or any other cell capable of lineage specific differentiation. Specifically described are methods to direct the lineage specific differentiation of hESC and/or hiPSC to nociceptors (i.e. nociceptor cells) using novel culture conditions. The nociceptors made using the methods of the present invention are further contemplated for various uses including, but limited to, use in in vitro drug discovery assays, pain research, and as a therapeutic to reverse disease of, or damage to, the peripheral nervous system (PNS). Further, compositions and methods are provided for producing melanocytes from human pluripotent stem cells for use in disease modeling.

Abstract: The present invention relates to methods of isolating a purified or enriched population of cortical or striatal immature interneuron progenitor cells and the isolated purified or enriched population of immature interneuron progenitor cells. Methods of treating a condition mediated by a loss or deficiency of interneuron function using the purified or enriched population of immature interneuron progenitor cells are also disclosed.

Abstract: The present invention relates generally to the field of cell biology of stem cells, more specifically the directed differentiation of pluripotent or multipotent stem cells, including human embryonic stem cells (hESC), somatic stem cells, and induced human pluripotent stem cells (hiPSC) using novel culture conditions. Specifically, methods are provided for obtaining neural tissue, floor plate cells, and placode including induction of neural plate development in hESCs for obtaining midbrain dopamine (DA) neurons, motorneurons, and sensory neurons. Further, neural plate tissue obtained using methods of the present inventions are contemplated for use in co-cultures with other tissues as inducers for shifting differentiation pathways, i.e. patterning.

Abstract: The invention provides a method of culturing cells which includes a proliferating step in which the number of precursor cells is expanded and a differentiating step in which the expanded precursor cells develop into neuronal cells. The proliferating step includes the step of incubating the precursor cells in proliferating medium which includes basic fibroblast growth factor (bFGF). The differentiating step includes incubating the precursor cells in differentiation media in a manner effective to form a cellular aggregate that is not adhered to any surface of the incubation vessel. In a preferred embodiment, the cells arc incubated in a roller tube. The differentiation media can also include at least one differentiating agent. The invention also provides a method for treating a neurological disorder, such as Parkinson's disease, a method of introducing a gene product into a brain of a patient, an assay for neurologically active substances, and a cell culture.

Abstract: The present invention relates to the growth of cells in culture under conditions that promote cell survival, proliferation, and/or cellular differentiation. The present inventors have found that proliferation was promoted and apoptosis reduced when cells were grown in lowered oxygen as compared to environmental oxygen conditions traditionally employed in cell culture techniques. Further, the inventors found that differentiation of precursor cells to specific fates also was enhanced in lowered oxygen where a much greater number and fraction of dopaminergic neurons were obtained when mesencephalic precursors were expanded and differentiated in lowered oxygen conditions. Thus at more physiological oxygen levels the proliferation and differentiation of CNS precursors is enhanced, and lowered oxygen is a useful adjunct for ex vivo generation of specific neuron types. Methods and compositions exploiting these findings are described.

Abstract: The invention provides a method of culturing cells. The method generally includes live stages: (1) expansion of ES cells; (2) generation of embryoid bodies; (3) selection of CNS precursor cells; (4) expansion of CNS precursor cells; and (5) differentiation of CNS precursor cells. During the expansion phase, the CNS precursor cells are cultured in a media which includes at least one neurologic agent such as bFGF, SHH, and FGF-8. The expanded CNS precursors are differentiated by withdrawal of at least one neurologic agent, typically, bFGF. Preferably, the differentiation media includes ascorbic acid. The method of the invention can be used to culture a variety of cells, preferably neuronal cells, including, but not limited to dopaminergic neuron cells, cholinergic neuronal cells and serotonergic neuron cells.

Abstract: The present invention relates to the growth of cells in culture under conditions that promote cell survival, proliferation, and/or cellular differentiation. The present inventors have found that proliferation was promoted and apoptosis reduced when cells were grown in lowered oxygen as compared to environmental oxygen conditions traditionally employed in cell culture techniques. Further, the inventors found that differentiation of precursor cells to specific fates also was enhanced in lowered oxygen where a much greater number and fraction of dopaminergic neurons were obtained when mesencephalic precursors were expanded and differentiated in lowered oxygen conditions. Thus at more physiological oxygen levels the proliferation and differentiation of CNS precursors is enhanced, and lowered oxygen is a useful adjunct for ex vivo generation of specific neuron types. Methods and compositions exploiting these findings are described.

Abstract: The present invention provides methods of preparing mammalian cells and tissues for therapeutic and diagnostic purposes that are derived from ntES cells. The present invention further provides the mammalian cells and tissues themselves. In addition, methods of using the mammalian cells and tissues as a therapeutic agent or as a diagnostic are provided.