Specification of functional cranial placode derivatives from human pluripotent stem cells

    公开(公告)号:US11591567B2

    公开(公告)日:2023-02-28

    申请号:US16373026

    申请日:2019-04-02

    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.

    METHOD OF NOCICEPTOR DIFFERENTIATION OF HUMAN EMBRYONIC STEM CELLS AND USES THEREOF

    公开(公告)号:US20220186180A1

    公开(公告)日:2022-06-16

    申请号:US17559314

    申请日:2021-12-22

    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.

    MIDBRAIN DOPAMINE (DA) NEURONS FOR ENGRAFTMENT

    公开(公告)号:US20190211306A1

    公开(公告)日:2019-07-11

    申请号:US16353546

    申请日:2019-03-14

    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.

    MIDBRAIN DOPAMINE (DA) NEURONS FOR ENGRAFTMENT
    6.
    发明申请
    MIDBRAIN DOPAMINE (DA) NEURONS FOR ENGRAFTMENT 审中-公开
    中枢神经元(DA)神经元进行植入

    公开(公告)号:US20150010514A1

    公开(公告)日:2015-01-08

    申请号:US14356042

    申请日:2012-11-02

    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。

    SPECIFICATION OF FUNCTIONAL CRANIAL PLACODE DERIVATIVES FROM HUMAN PLURIPOTENT STEM CELLS

    公开(公告)号:US20190225939A1

    公开(公告)日:2019-07-25

    申请号:US16373026

    申请日:2019-04-02

    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.