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1.
公开(公告)号:US11591567B2
公开(公告)日:2023-02-28
申请号:US16373026
申请日:2019-04-02
发明人: Stuart Chambers , Lorenz Studer , Zehra Dincer , Bastian Zimmer
IPC分类号: C12N5/0793 , A61K35/12 , C07D211/00 , C07D307/32 , C07D243/36
摘要: Cranial placodes are embryonic structures essential for sensory and endocrine organ development. The efficient derivation of cranial placodes from human pluripotent stem cells is disclosed where the timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Further fate specification at the pre-placode stage enables the selective generation of placode-derived trigeminal ganglia capable of in vivo engraftment, mature lens fibers and anterior pituitary hormone-producing cells that upon transplantation produce hormones including, but not limited to, human growth hormone and adrenocortiocotropic hormone in vivo. Alternatively, anterior pituitary hormone-producing cells are generated in cell culture systems in vitro.
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公开(公告)号:US20220186180A1
公开(公告)日:2022-06-16
申请号:US17559314
申请日:2021-12-22
IPC分类号: C12N5/0793 , C12N5/079 , G01N33/50 , C12N5/071
摘要: 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.
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公开(公告)号:US20210123018A1
公开(公告)日:2021-04-29
申请号:US17093126
申请日:2020-11-09
发明人: Lorenz Studer , Stefan Irion , Mark Tomishima , Sonja Kriks
IPC分类号: C12N5/0793 , A61K35/30 , A61K35/545 , A61P25/16
摘要: The presently disclosed subject matter provides for in vitro methods of inducing differentiation of human stem cells into midbrain dopamine neurons, and precursors thereof, and cells generated by such methods. The presently disclosed subject matter also provides for uses of such cells for treating neurodegenerative disorders.
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公开(公告)号:US20190211306A1
公开(公告)日:2019-07-11
申请号:US16353546
申请日:2019-03-14
发明人: Lorenz Studer , Jae-Won Shim , Sonja Kriks
IPC分类号: C12N5/0793 , A61K35/30 , C12N5/0797
摘要: 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.
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公开(公告)号:US20170159012A1
公开(公告)日:2017-06-08
申请号:US14169286
申请日:2014-01-31
发明人: Stuart Chambers , Lorenz Studer
IPC分类号: C12N5/0793
CPC分类号: C12N5/0619 , C12N2500/90 , C12N2501/15 , C12N2501/155 , C12N2501/41 , C12N2501/415 , C12N2501/60 , C12N2501/998 , C12N2506/02 , C12N2506/45
摘要: 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.
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公开(公告)号:US20150010514A1
公开(公告)日:2015-01-08
申请号:US14356042
申请日:2012-11-02
发明人: Lorenz Studer , Jae-Won Shim , Sonja Kriks
IPC分类号: C12N5/0793 , C12N5/0797 , A61K35/30
CPC分类号: C12N5/0619 , A61K35/30 , C12N5/0623 , C12N2501/01 , C12N2501/119 , C12N2501/13 , C12N2501/15 , C12N2501/16 , C12N2501/41 , C12N2501/415 , C12N2501/999 , C12N2506/02 , C12N2506/45
摘要: 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.
摘要翻译: 本发明涉及干细胞生物学领域,特别是多能干细胞或多能干细胞的谱系特异性分化,其可以包括但不限于人类胚胎干细胞(hESC)以及非胚胎人诱导多能干细胞 细胞(hiPSC),体细胞干细胞,来自患有疾病的患者的干细胞,或任何其他能够谱系特异性分化的细胞。 具体描述的是使用新的培养条件将hESC和/或hiPSC的谱系特异性分化引导到地板中脑祖细胞中,然后进一步转化成大量中脑命运FOXA2 + LMX1A + TH +多巴胺(DA)神经元的方法。 使用本发明的方法制备的中脑命运FOXA2 + LMX1A + TH +多巴胺(DA)神经元进一步考虑了各种用途,包括但不限于用于体外药物发现测定,神经学研究和作为治疗剂 逆转疾病或损害患者多巴胺神经元的缺乏。 此外,提供组合物和方法用于区分来自人多能干细胞的中脑命运FOXA2 + LMX1A + TH +多巴胺(DA)神经元用于疾病建模,特别是帕金森病。 另外,正常的DA神经元富集标记,如CD142和A9型神经元细胞。
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7.
公开(公告)号:US20190225939A1
公开(公告)日:2019-07-25
申请号:US16373026
申请日:2019-04-02
发明人: Stuart Chambers , Lorenz Studer , Zehra Dincer , Bastian Zimmer
IPC分类号: C12N5/0793 , A61K35/12
摘要: Cranial placodes are embryonic structures essential for sensory and endocrine organ development. The efficient derivation of cranial placodes from human pluripotent stem cells is disclosed where the timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Further fate specification at the pre-placode stage enables the selective generation of placode-derived trigeminal ganglia capable of in vivo engraftment, mature lens fibers and anterior pituitary hormone-producing cells that upon transplantation produce hormones including, but not limited to, human growth hormone and adrenocortiocotropic hormone in vivo. Alternatively, anterior pituitary hormone-producing cells are generated in cell culture systems in vitro.
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公开(公告)号:US20190093074A1
公开(公告)日:2019-03-28
申请号:US16199801
申请日:2018-11-26
发明人: Lorenz Studer , Nadja Zeltner
IPC分类号: C12N5/0793 , C12N5/0775 , A61K35/30 , A61P25/28 , C12N5/074
摘要: The presently disclosed subject matter provides for in vitro methods of inducing differentiation of stem cells (e.g., human stem cells) into proprioceptors, proprioceptors generated by such methods, and compositions comprising such proprioceptors. The presently disclosed subject matter also provides for uses of such proprioceptors for preventing and/or treating disorders of proprioceptor neurons and/or neurodegenerative disorders (e.g., Friedreich's Ataxia).
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公开(公告)号:US20180291339A1
公开(公告)日:2018-10-11
申请号:US16015748
申请日:2018-06-22
发明人: Lorenz Studer , Faranak Fattahi
IPC分类号: C12N5/0793 , A61K35/30
摘要: The presently disclosed subject matter provides for in vitro methods of inducing differentiation of stem cells into enteric neural crest lineage cells, and enteric neural crest lineage cells by such methods. The presently disclosed subject matter also provides for uses of such enteric neural crest lineage cells for preventing and/or treating enteric nervous system disorders (e.g, Hirschsprung's disease), and for screening compounds suitable for preventing and/or treating enteric nervous system disorders (e.g., Hirschsprung's disease).
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公开(公告)号:US20180237748A9
公开(公告)日:2018-08-23
申请号:US14168835
申请日:2014-01-30
发明人: Stuart Chambers , Lorenz Studer
IPC分类号: C12N5/0793
CPC分类号: C12N5/0619 , C12N2500/90 , C12N2501/15 , C12N2501/155 , C12N2501/41 , C12N2501/415 , C12N2501/60 , C12N2501/998 , C12N2506/02 , C12N2506/45
摘要: 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.
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