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1. 发明授权

US08709807B2 Method of isolating human neuroepithelial precursor cells from human fetal tissue 有权
标题翻译：从人胎儿组织中分离人神经上皮前体细胞的方法
公开(公告)号：US08709807B2
公开(公告)日：2014-04-29
申请号：US13435424
申请日：2012-03-30
申请人： Margot Mayer-Proschel , Mahendra S. Rao , Patrick A. Tresco , Darin J. Messina
发明人： Margot Mayer-Proschel , Mahendra S. Rao , Patrick A. Tresco , Darin J. Messina
IPC分类号： C12N5/08 , C12N5/0797
CPC分类号： A61K35/54 , A61K35/12 , C12N5/0623
摘要： A method for isolating human neuroepithelial precursor cells from human fetal tissue by culturing the human fetal cells in fibroblast growth factor and chick embryo extract and immunodepleting from the cultured human fetal cells any cells expressing A2B5, NG2 and eNCAM is provided. In addition, methods for transplanting these cells into an animal are provided. Animals models transplanted with these human neuroepithelial precursor cells and methods for monitoring survival, proliferation, differentiation and migration of the cells in the animal model via detection of human specific markers are also provided.
摘要翻译：通过培养成纤维细胞生长因子和雏鸡胚胎提取物中的人胎细胞和从培养的人胎儿细胞免疫进行分离，可以提供任何表达A2B5，NG2和eNCAM的细胞从人胎儿组织中分离人神经上皮前体细胞的方法。另外，提供将这些细胞移植到动物体内的方法。还提供了用这些人类神经上皮前体细胞移植的动物模型以及通过检测人特异性标志物监测动物模型中细胞的存活，增殖，分化和迁移的方法。

2. 发明授权

US06787353B1 Lineage-restricted neuronal precursors and methods of isolation 失效
标题翻译：谱系限制性神经元前体和分离方法
公开(公告)号：US06787353B1
公开(公告)日：2004-09-07
申请号：US09109858
申请日：1998-07-02
申请人： Mahendra S. Rao , Margot Mayer-Proschel , Anjali J. Kalyani
发明人： Mahendra S. Rao , Margot Mayer-Proschel , Anjali J. Kalyani
IPC分类号： C12N508
CPC分类号： C12N5/0623 , A61K35/12 , A61K48/00 , C12N2501/115 , C12N2501/13 , C12N2501/385
摘要： A self-renewing restricted stem cell population has been identified in developing (embryonic day 13.5) spinal cords that can differentiate into multiple neuronal phenotypes, but cannot differentiate into glial phenotypes. This neuronal-restricted precursor (NRP) expresses highly polysialated or embryonic neural cell adhesion molecule (E-NCAM) and is morphologically distinct from neuroepithelial stem cells (NEP cells) and spinal glial progenitors derived from embryonic day 10.5 spinal cord. NRP cells self renew over multiple passages in the presence of fibroblast growth factor (FGF) and neurotrophin 3 (NT-3) and express a characteristic subset of neuronal epitopes. When cultured in the presence of RA and the absence of FGF, NRP cells differentiate into GABAergic, glutaminergic, and cholinergic immunoreactive neurons. NRP cells can also be generated from multipotent NEP cells cultured from embryonic day 10.5 neural tubes. Clonal analysis shows that E-NCAM immunoreactive NRP cells arise from an NEP progenitor cell that generates other restricted CNS precursors. The NEP-derived E-NCAM immunoreactive cells undergo self renewal in defined medium and differentiate into multiple neuronal phenotypes in mass and clonal culture. Thus, a direct lineal relationship exists between multipotential NEP cells and more restricted neuronal precursor cells present in vivo at embryonic day 13.5 in the spinal cord. Methods for treating neurological diseases are also disclosed.
摘要翻译：在发育（胚胎期13.5）脊髓中已经鉴定出自我更新的限制性干细胞群，其可以分化成多个神经元表型，但不能分化成胶质表型。这种神经元限制性前体（NRP）表达高度多聚化或胚胎神经细胞粘附分子（E-NCAM），并且在形态学上与神经上皮干细胞（NEP细胞）和源自胚胎第10.5天脊髓的脊髓神经祖细胞不同。 NRP细胞在成纤维细胞生长因子（FGF）和神经营养因子3（NT-3）的存在下自我更新多次，并表达神经元表位的特征亚群。当在RA和无FGF的存在下培养时，NRP细胞分化为GABA能，谷氨酸能和胆碱能免疫反应性神经元。 NRP细胞还可以从从胚胎第10.5天神经管培养的多能NEP细胞产生。克隆分析表明，E-NCAM免疫反应性NRP细胞来自产生其他受限制的CNS前体的NEP祖细胞。 NEP衍生的E-NCAM免疫反应性细胞在限定的培养基中进行自我更新，并在大量和克隆培养中分化成多个神经元表型。因此，多潜能NEP细胞与脊髓中第13.5天体内存在的更多受限的神经元前体细胞之间存在直接的直线关系。还公开了治疗神经疾病的方法。

3. 发明授权

US07795021B2 Lineage restricted glial precursors from the central nervous system 有权
标题翻译：谱系受限于神经胶质前体从中枢神经系统
公开(公告)号：US07795021B2
公开(公告)日：2010-09-14
申请号：US11694221
申请日：2007-03-30
申请人： Mahendra S. Rao , Mark Noble , Margot Mayer-Proschel
发明人： Mahendra S. Rao , Mark Noble , Margot Mayer-Proschel
IPC分类号： C12N5/06
CPC分类号： G01N33/5058 , A61K35/12 , C12N5/0622 , C12N5/0623 , C12N2501/135 , C12N2501/395 , C12N2503/02 , C12N2506/02 , C12N2510/00
摘要： A glial precursor cell population from mammalian central nervous system has been isolated. These A2B5+ E-NCAM− glial-restricted precursor (GRP) cells are capable of differentiating into oligodendrocytes, A2B5+ process-bearing astrocytes, and A2B5− fibroblast-like astrocytes, but not into neurons. GRP cells can be maintained by regeneration in culture. GRP cells differ from oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells in growth factor requirements, morphology, and progeny. Methods of use of GRP cells are also disclosed.
摘要翻译：已经分离出来自哺乳动物中枢神经系统的胶质前体细胞群。这些A2B5 + E-NCAM-胶质细胞限制性前体（GRP）细胞能够分化为少突胶质细胞，A2B5 +过程的星形胶质细胞和A2B5-成纤维细胞样星形胶质细胞，但不能分化为神经元。 GRP细胞可通过培养中的再生来维持。 GRP细胞不同于少突胶质细胞-2型星形胶质细胞（O-2A）祖细胞的生长因子要求，形态和后代。还公开了使用GRP细胞的方法。

4. 发明授权

US06852532B2 Method of isolating human neuroepithelial precursor cells from human fetal tissue 失效
标题翻译：从人胎儿组织中分离人神经上皮前体细胞的方法
公开(公告)号：US06852532B2
公开(公告)日：2005-02-08
申请号：US09813429
申请日：2001-03-21
申请人： Margot Mayer-Proschel , Mahendra S. Rao , Patrick A. Tresco , Darin J. Messina
发明人： Margot Mayer-Proschel , Mahendra S. Rao , Patrick A. Tresco , Darin J. Messina
IPC分类号： A61K35/12 , C12N5/0797 , C12N5/00 , C12N5/08
CPC分类号： A61K35/54 , A61K35/12 , C12N5/0623
摘要： A method for isolating human neuroepithelial precursor cells from human fetal tissue by culturing the human fetal cells in fibroblast growth factor and chick embryo extract and immunodepleting from the cultured human fetal cells any cells expressing A2B5, NG2 and eNCAM is provided. In addition, methods for transplanting these cells into an animal are provided. Animals models transplanted with these human neuroepithelial precursor cells and methods for monitoring survival, proliferation, differentiation and migration of the cells in the animal model via detection of human specific markers are also provided.
摘要翻译：通过培养成纤维细胞生长因子和雏鸡胚胎提取物中的人胎细胞和从培养的人胎儿细胞免疫进行分离，可以提供任何表达A2B5，NG2和eNCAM的细胞从人胎儿组织中分离人神经上皮前体细胞的方法。另外，提供将这些细胞移植到动物体内的方法。还提供了用这些人类神经上皮前体细胞移植的动物模型以及通过检测人特异性标志物监测动物模型中细胞的存活，增殖，分化和迁移的方法。

5. 发明申请

US20100015702A1 Generation, Characterization and Isolation of Neuroepithelial Stem Cells and Lineage Restricted Intermediate Precursor 审中-公开
标题翻译：神经上皮干细胞和谱系限制性中间体前体的产生，表征和分离
公开(公告)号：US20100015702A1
公开(公告)日：2010-01-21
申请号：US12568419
申请日：2009-09-28
申请人： Mahendra S. Rao , Margot Mayer-Proschel
发明人： Mahendra S. Rao , Margot Mayer-Proschel
IPC分类号： C12N5/00
CPC分类号： C12N5/0661 , C12N5/0623 , C12N2501/113 , C12N2501/115 , C12N2501/135 , C12N2501/155 , C12N2501/385 , C12N2506/08
摘要： Multipotent neuroepithelial stem cells and lineage-restricted oligodendrocyte-astrocyte precursor cells are described. The neuroepithelial stem cells are capable of self-renewal and of differentiation into neurons, astrocytes, and oligodendrocytes. The oligodendrocyte-astrocyte precursor cells are derived from neuroepithelial stem cells, are capable of self-renewal, and can differentiate into oligodendrocytes and astrocytes, but not neurons. Methods of generating, isolating, and culturing such neuroepithelial stem cells and oligodendrocyte-astrocyte precursor cells are also disclosed.
摘要翻译：描述了多能神经上皮干细胞和谱系限制性少突胶质细胞 - 星形胶质细胞前体细胞。神经上皮干细胞能够自我更新并分化为神经元，星形胶质细胞和少突胶质细胞。少突胶质细胞 - 星形胶质细胞前体细胞衍生自神经上皮干细胞，能够自我更新，并能分化为少突胶质细胞和星形胶质细胞，而不能分化为神经元。还公开了产生，分离和培养这种神经上皮干细胞和少突胶质细胞 - 星形胶质细胞前体细胞的方法。

6. 发明申请

US20090162330A1 Method of Isolating Human Neuroepithelial Precursor Cells from Human Fetal Tissue 有权
标题翻译：人类胎盘组织分离人神经上皮前体细胞的方法
公开(公告)号：US20090162330A1
公开(公告)日：2009-06-25
申请号：US12395677
申请日：2009-03-01
申请人： Margot Mayer-Proschel , Mahendra S. Rao , Patrick A. Tresco , Darin J. Messina
发明人： Margot Mayer-Proschel , Mahendra S. Rao , Patrick A. Tresco , Darin J. Messina
IPC分类号： A61K45/00 , G01N33/53 , A61P25/28
CPC分类号： A61K35/54 , A61K35/12 , C12N5/0623
摘要： A method for isolating human neuroepithelial precursor cells from human fetal tissue by culturing the human fetal cells in fibroblast growth factor and chick embryo extract and immunodepleting from the cultured human fetal cells any cells expressing A2B5, NG2 and eNCAM is provided. In addition, methods for transplanting these cells into an animal are provided. Animals models transplanted with these human neuroepithelial precursor cells and methods for monitoring survival, proliferation, differentiation and migration of the cells in the animal model via detection of human specific markers are also provided.
摘要翻译：通过培养成纤维细胞生长因子和雏鸡胚胎提取物中的人胎细胞和从培养的人胎儿细胞免疫进行分离，可以提供任何表达A2B5，NG2和eNCAM的细胞从人胎儿组织中分离人神经上皮前体细胞的方法。另外，提供将这些细胞移植到动物体内的方法。还提供了用这些人类神经上皮前体细胞移植的动物模型以及通过检测人特异性标志物监测动物模型中细胞的存活，增殖，分化和迁移的方法。

7. 发明授权

US07037720B2 Neuroepithelial stem cells and glial-restricted intermediate precursors 失效
公开(公告)号：US07037720B2
公开(公告)日：2006-05-02
申请号：US10025333
申请日：2001-12-19
申请人： Mahendra S. Rao , Margot Mayer-Proschel
发明人： Mahendra S. Rao , Margot Mayer-Proschel
IPC分类号： C12N5/06
CPC分类号： C12N5/0661 , C12N5/0623 , C12N2501/113 , C12N2501/115 , C12N2501/135 , C12N2501/155 , C12N2501/385 , C12N2506/08
摘要： Multipotent neuroepithelial stem cells and lineage-restricted oligodendrocyte-astrocyte precursor cells are described. The neuroepithelial stem cells are capable of self-renewal and of differentiation into neurons, astrocytes, and oligodendrocytes. The oligodendrocyte-astrocyte precursor cells are derived from neuroepithelial stem cells, are capable of self-renewal, and can differentiate into oligodendrocytes and astrocytes, but not neurons. Methods of generating, isolating, and culturing such neuroepithelial stem cells and oligodendrocyte-astrocyte precursor cells are also disclosed.

8. 发明授权

US06235527B1 Lineage restricted glial precursors from the central nervous system 失效
公开(公告)号：US06235527B1
公开(公告)日：2001-05-22
申请号：US08980850
申请日：1997-11-29
申请人： Mahendra S. Rao , Mark Noble , Margot Mayer-Proschel
发明人： Mahendra S. Rao , Mark Noble , Margot Mayer-Proschel
IPC分类号： C12N506
CPC分类号： G01N33/5058 , A61K35/12 , C12N5/0622 , C12N5/0623 , C12N2501/135 , C12N2501/395 , C12N2503/02 , C12N2506/02 , C12N2510/00
摘要： A glial precursor cell population from mammalian central nervous system has been isolated. These A2B5+ E-NCAM− glial-restricted precursor (GRP) cells are capable of differentiating into oligodendrocytes, A2B5+ process-bearing astrocytes, and A2B5− fibroblast-like astrocytes, but not into neurons. GRP cells can be maintained by regeneration in culture. GRP cells differ from oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells in growth factor requirements, morphology, and progeny. Methods of use of GRP cells are also disclosed.

9. 发明申请

US20130017179A1 Lineage-Restricted Neuronal Precursors 审中-公开
标题翻译：血缘限制性神经元前体
公开(公告)号：US20130017179A1
公开(公告)日：2013-01-17
申请号：US13606355
申请日：2012-09-07
申请人： Mahendra S. Rao , Margot Mayer-Proschel , Anjali J. Kalyani
发明人： Mahendra S. Rao , Margot Mayer-Proschel , Anjali J. Kalyani
IPC分类号： C12N5/07 , A61P25/28 , G01N33/567 , A61K35/12 , C12Q1/02
CPC分类号： C12N5/0623 , A61K35/12 , A61K48/00 , C12N2501/115 , C12N2501/13 , C12N2501/385
摘要： A cell population has been identified and isolated that can differentiate into multiple neuronal phenotypes, but cannot differentiate into glial phenotypes. This mammalian CNS neuron-restricted cell expresses highly polysialated or embryonic neural cell adhesion molecule (E-NCAM) and is morphologically distinct from neuroepithelial stem cells (NEP cells) and spinal glial progenitors derived from embryonic day 10.5 spinal cord. Methods for isolating these cells and uses thereof are also disclosed.
摘要翻译：已经鉴定和分离了可以分化成多个神经元表型的细胞群，但不能分化成胶质表型。这种哺乳动物CNS神经元限制性细胞表达高度多聚化或胚胎神经细胞粘附分子（E-NCAM），并且在形态上不同于神经上皮干细胞（NEP细胞）和源自胚胎第10.5天脊髓的脊髓神经祖细胞。还公开了分离这些细胞的方法及其用途。

10. 发明申请

US20120321705A1 Lineage Restricted Glial Precursors from the Central Nervous System 审中-公开
标题翻译：来自中枢神经系统的血缘限制性神经胶质前体
公开(公告)号：US20120321705A1
公开(公告)日：2012-12-20
申请号：US13593847
申请日：2012-08-24
申请人： Mahendra S. Rao , Mark Noble , Margot Mayer-Proschel
发明人： Mahendra S. Rao , Mark Noble , Margot Mayer-Proschel
IPC分类号： C12N5/0797 , A61P25/28 , G01N33/566 , A61K9/48 , C12Q1/68 , A61K35/30 , A61P25/00
CPC分类号： G01N33/5058 , A61K35/12 , C12N5/0622 , C12N5/0623 , C12N2501/135 , C12N2501/395 , C12N2503/02 , C12N2506/02 , C12N2510/00
摘要： A glial precursor cell population from mammalian central nervous system has been isolated. These A2B5+ E-NCAM− glial-restricted precursor (GRP) cells are capable of differentiating into oligodendrocytes, A2B5+ process-bearing astrocytes, and A2B5− fibroblast-like astrocytes, but not into neurons. GRP cells can be maintained by regeneration in culture. GRP cells differ from oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells in growth factor requirements, morphology, and progeny. Methods of use of GRP cells are also disclosed.
摘要翻译：已经分离出来自哺乳动物中枢神经系统的胶质前体细胞群。这些A2B5 + E-NCAM-胶质细胞限制性前体（GRP）细胞能够分化为少突胶质细胞，A2B5 +过程的星形胶质细胞和A2B5-成纤维细胞样星形胶质细胞，但不能分化为神经元。 GRP细胞可通过培养中的再生来维持。 GRP细胞不同于少突胶质细胞-2型星形胶质细胞（O-2A）祖细胞的生长因子要求，形态和后代。还公开了使用GRP细胞的方法。

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