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1. 发明申请

US20060104962A1 Transfected hematopoietic stem cells and methods of treatment of neovascular eye diseases therewith 审中-公开
标题翻译：转染的造血干细胞及其治疗新生血管性眼病的方法
公开(公告)号：US20060104962A1
公开(公告)日：2006-05-18
申请号：US11168010
申请日：2005-06-28
申请人： Martin Friedlander , Atsushi Otani , Karen Silva , Stacey Moreno
发明人： Martin Friedlander , Atsushi Otani , Karen Silva , Stacey Moreno
IPC分类号： A61K48/00 , C12N5/08
CPC分类号： C12N5/0647 , A61K38/00 , A61K48/00 , A61K2035/124 , C12N5/0692
摘要： Transfected, mammalian, adult bone marrow-derived, lineage negative hematopoietic stem cell populations (Lin−HSCs) contain endothelial progenitor cells (EPCs) capable of rescuing retinal blood vessels and neuronal networks in the eye and a gene operably encoding an antiangiogenic fragment of tryptophanyl tRNA synthetase (TrpRS). Preferably at least about 20% of the cells in the transfected Lin−HSC population express the cell surface antigen CD31. The transfected Lin−HSC populations are useful for treatment of ocular vascular diseases. In a preferred embodiment, the Lin−HSCs are isolated by extracting bone marrow from an adult mammal; separating a plurality of monocytes from the bone marrow; labeling the monocytes with biotin-conjugated lineage panel antibodies to one or more lineage surface antigens; removing of monocytes that are positive for the lineage surface antigens from the plurality of monocytes, recovering a Lin−HSC population containing EPCs, and transfecting the recovered cells with DNA operably encoding an antiangiogenic fragment of TrpRS. Methods of preparing transfected stem cell populations of the invention, and methods of treating ocular diseases and injury are also described.
摘要翻译：转染的哺乳动物，成年骨髓来源的谱系负造血干细胞群体（含有HSCs）含有能够拯救眼睛中的视网膜血管和神经元网络的内皮祖细胞（EPCs）和基因可操作地编码色氨酸tRNA合成酶（TrpRS）的抗血管生成片段。优选地，转染的LINH-HSC群体中至少约20％的细胞表达细胞表面抗原CD31。转染的HSP-HSC群体可用于治疗眼血管疾病。在一个优选实施方案中，通过从成年哺乳动物中提取骨髓来分离骨髓间充质干细胞; 从骨髓中分离多个单核细胞; 用与生物素缀合的谱系抗体对一种或多种谱系表面抗原标记单核细胞; 从多个单核细胞中除去对于谱系表面抗原呈阳性的单核细胞，回收含有EPCs的LinC-HSC群体，并用可操作地编码TrpRS抗血管生成片段的DNA转染回收的细胞。还描述了制备本发明的转染干细胞群体的方法，以及治疗眼部疾病和损伤的方法。

2. 发明申请

US20060104963A1 Treatment of cone cell degeneration with transfected lineage negative hematopoietic stem cells 审中-公开
标题翻译：用转染谱系阴性造血干细胞治疗锥细胞变性
公开(公告)号：US20060104963A1
公开(公告)日：2006-05-18
申请号：US11168130
申请日：2005-06-28
申请人： Martin Friedlander , Atsushi Otani , Karen Silva , Stacey Moreno
发明人： Martin Friedlander , Atsushi Otani , Karen Silva , Stacey Moreno
IPC分类号： A61K48/00 , C12N5/06 , C12N5/08
CPC分类号： C12N5/0647 , A61K38/00 , A61K48/00 , A61K2035/124 , C12N5/0692
摘要： Transfected, mammalian, adult bone marrow-derived, lineage negative hematopoietic stem cell populations (Lin− HSCs) contain endothelial progenitor cells (EPCs) capable of rescuing retinal blood vessels and neuronal networks in the eye. Preferably at least about 20% of the cells express the cell surface antigen CD31. The transfected stem cells express an antiangiogenic fragment of tryptophanyl tRNA synthetase (TrpRS). The transfected Lin− HSC populations are useful for treatment of ocular vascular diseases and to ameliorate cone cell degeneration in the retina. In a preferred embodiment, the Lin− HSCs are isolated by extracting bone marrow from an adult mammal; separating a plurality of monocytes from the bone marrow; labeling the monocytes with biotin-conjugated lineage panel antibodies to one or more lineage surface antigens; removing of monocytes that are positive for the lineage surface antigens from the plurality of monocytes, and recovering a Lin− HSC population containing EPCs. The treatment may be enhanced by stimulating proliferation of activated astrocytes in the retina using a laser.
摘要翻译：转染的哺乳动物，成年骨髓来源的血清造血干细胞群体（含有HSCs）含有能够拯救眼睛中视网膜血管和神经元网络的内皮祖细胞（EPCs）。优选地，至少约20％的细胞表达细胞表面抗原CD31。转染的干细胞表达色氨酸tRNA合成酶（TrpRS）的抗血管生成片段。转染的HSH-HSC群体可用于治疗眼血管疾病并改善视网膜中的锥细胞变性。在一个优选实施方案中，通过从成年哺乳动物中提取骨髓来分离骨髓间充质干细胞; 从骨髓中分离多个单核细胞; 用与生物素缀合的谱系抗体对一种或多种谱系表面抗原标记单核细胞; 从多个单核细胞中除去对于谱系表面抗原呈阳性的单核细胞，以及回收含有EPCs的LINC-HSC群体。可以通过使用激光刺激视网膜中活化的星形胶质细胞的增殖来增强治疗。

3. 发明申请

US20070231310A1 Treatment of cone cell degeneration with transfected lineage negative hematopoietic stem cells 审中-公开
标题翻译：用转染谱系阴性造血干细胞治疗锥细胞变性
公开(公告)号：US20070231310A1
公开(公告)日：2007-10-04
申请号：US11788973
申请日：2007-04-23
申请人： Martin Friedlander , Atsushi Otani , Karen Silva , Stacey (Hanekamp) Moreno
发明人： Martin Friedlander , Atsushi Otani , Karen Silva , Stacey (Hanekamp) Moreno
IPC分类号： A61K48/00
CPC分类号： C12N5/0647 , A61K38/00 , A61K48/00 , A61K2035/124 , C12N5/0692
摘要： A method of preserving cone cells in the eye of a mammal suffering from a retinal degenerative disease comprises isolating from the bone marrow of the mammal a lineage negative hematopoietic stem cell population that includes endothelial progenitor cells, transfecting cells from the stem cell population with a gene that operably encodes an antiangiogenic fragment of human tryptophanyl tRNA synthetase (TrpRS), and subsequently intravitreally injecting the transfected cells into the eye of the mammal in an amount sufficient to inhibit the degeneration of cone cells in the retina of the eye. The treatment may be enhanced by stimulating proliferation of activated astrocytes in the retina using a laser.
摘要翻译：维持患有视网膜退行性疾病的哺乳动物眼睛中的锥形细胞的方法包括从哺乳动物的骨髓中分离出含有内皮祖细胞的谱系负造血干细胞群，用基因转染干细胞群体的细胞可操作地编码人色氨酰tRNA合成酶（TrpRS）的抗血管生成片段，随后以足以抑制眼睛视网膜中锥细胞退化的量将经转染的细胞玻璃体内注射到哺乳动物的眼中。可以通过使用激光刺激视网膜中活化的星形胶质细胞的增殖来增强治疗。

4. 发明申请

US20070116685A1 Hematopoietic stem cells and methods of treatment of neovascular eye diseases therewith 审中-公开
标题翻译：造血干细胞及其治疗新生血管性眼病的方法
公开(公告)号：US20070116685A1
公开(公告)日：2007-05-24
申请号：US11643571
申请日：2006-12-20
申请人： Martin Friedlander , Atsushi Otani , Karen Silva
发明人： Martin Friedlander , Atsushi Otani , Karen Silva
IPC分类号： A61K35/14 , C12N5/06 , C12N5/08
CPC分类号： C12N5/0692 , A61K48/00 , A61K2035/124 , C12N5/0647
摘要： Isolated, mammalian, bone marrow-derived, hematopoietic stem cell populations contain endothelial progenitor cells (EPC) capable of forming retinal blood vessels. At least about 50% of the cells in the isolated cell population express CD31 and c-kit. Up to about 8% of the cells can express Sca-1, and up to about 4% of the cells can express Flk-1/KDR. The cells can incorporate into the vasculature of the retina when intravitreally injected into the eye, and can thereby stabilize or rebuilt diseased or abnormal retinal blood vessels.
摘要翻译：分离的，哺乳动物，骨髓来源的造血干细胞群含有能够形成视网膜血管的内皮祖细胞（EPC）。分离的细胞群中至少约50％的细胞表达CD31和c-kit。高达约8％的细胞可以表达Sca-1，最多约4％的细胞可以表达Flk-1 / KDR。当玻璃体内注射到眼睛中时，细胞可以并入视网膜的脉管系统中，从而可以稳定或重建患病或异常的视网膜血管。

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