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    Method of stem cell delivery into the brain during chronic disease using blood brain barrier permeabilizers
    11.
    发明授权
    Method of stem cell delivery into the brain during chronic disease using blood brain barrier permeabilizers 有权

    公开(公告)号：US10765706B2

    公开(公告)日：2020-09-08

    申请号：US15257315

    申请日：2016-09-06

    申请人： Cesario Venturina Borlongan ,  Paul R. Sanberg

    发明人： Cesario Venturina Borlongan ,  Paul R. Sanberg

    IPC分类号： A61K35/51 ,  A61K47/26 ,  A61K9/00

    摘要： Blood brain barrier (BBB) permeabilizers, such as mannitol, can facilitate the entry of stem cells from the periphery to the stroke brain. It is unknown whether BBB permeation in the chronic stage of the disease still facilitates the entry of stem cells from the periphery to the injured brain. Evidence herein shows BBB permeation in the chronic stage of stroke assisted in the entry of stem cells from the periphery to the stroke brain. Stroke models treated with human umbilical cord stem cells (hUCBC) only (2 million viable cells), mannitol or a combination. Results revealed that hUCBC alone or combined with mannitol displayed significant behavioral and histological deficits compared to control animals, with the HUCBC-mannitol combined treatment showing improvements over hUCBC only treatments in brain cell survival in the peri-infarct area. BBB permeation in chronic stroke also lowers the effective stem cell dose necessary to improve functional outcomes.

    PLASMA DERIVED FROM HUMAN UMBILICAL CORD BLOOD FOR THE TREATMENT OF NEURODEGENERATIVE DISORDERS
    12.
    发明申请
    PLASMA DERIVED FROM HUMAN UMBILICAL CORD BLOOD FOR THE TREATMENT OF NEURODEGENERATIVE DISORDERS 审中-公开

    公开(公告)号：US20200061123A1

    公开(公告)日：2020-02-27

    申请号：US16655506

    申请日：2019-10-17

    申请人： Svitlana Garbuzova-Davis ,  Jared Carl Ehrhart ,  Paul R. Sanberg

    发明人： Svitlana Garbuzova-Davis ,  Jared Carl Ehrhart ,  Paul R. Sanberg

    IPC分类号： A61K35/51 ,  A61P25/28 ,  C12N5/0775

    摘要： A method of treating neurodegenerative diseases using hUCB plasma is presented herein. hUCB plasma attenuated the hyperactive response (Group III) and potentiated the normal response in Group I ALS patients, but did not alter that of the non-responders to PHA (Group II). The elevated activity of caspase 3/7 observed in the MNCs from ALS patients was significantly reduced by hUCB plasma treatment. The ability of hUCB plasma to modulate the mitogen cell response and reduce caspase activity suggest that the use of hUCB plasma alone, or with stem cells, may prove useful as a therapeutic in ALS patients. hUCB plasma was shown to increase therapeutic efficacy of MNCs as well as decrease apoptosis of MNCs. The cytokine profile of hUCB plasma supports its usefulness as a sole therapeutic as well as an additive to MNCs.

    HUMAN UMBILICAL CORD BLOOD-DERIVED MONOCYTES FOR TREATMENT OF NEURODEGENERATIVE DISEASES AND DISORDERS
    13.
    发明申请
    HUMAN UMBILICAL CORD BLOOD-DERIVED MONOCYTES FOR TREATMENT OF NEURODEGENERATIVE DISEASES AND DISORDERS 审中-公开

    公开(公告)号：US20170143769A1

    公开(公告)日：2017-05-25

    申请号：US15360023

    申请日：2016-11-23

    申请人： Jun Tan ,  Paul R. Sanberg

    发明人： Jun Tan ,  Paul R. Sanberg

    IPC分类号： A61K35/51 ,  A61K9/00

    CPC分类号： A61K35/51 ,  A61K35/15 ,  A61K2035/124

    摘要： Human umbilical cord blood-derived monocytes that markedly promote Aβ clearance through heterodimerization of sAPPα with Aβ and resultant sAPPα production for prevention or treatment of Alzheimer's disease and other neurodegenerative disorders (including stroke and TBI). It was discovered that multiple low-dose infusions of human umbilical cord blood cells (HUCBCs) ameliorate cognitive impairments and reduce Aβ-associated neuropathology in PSAPP transgenic mice, which markedly promotes amyloid precursor protein (APP) α-cleavage and resultant sAPPα production for pharmaceutical purposes, in particular for treating or slowing the progression of Alzheimer's disease.

    HUCBC TREATMENT OF AMYLOID-ASSOCIATED DISEASE
    14.
    发明申请
    HUCBC TREATMENT OF AMYLOID-ASSOCIATED DISEASE 审中-公开
    琥珀酸相关疾病的HUCBC治疗

    公开(公告)号：US20160303165A1

    公开(公告)日：2016-10-20

    申请号：US15195243

    申请日：2016-06-28

    申请人： Jun Tan ,  Paul R. Sanberg

    发明人： Jun Tan ,  Paul R. Sanberg

    IPC分类号： A61K35/16

    CPC分类号： A61K35/16 ,  A61K35/44 ,  A61K2035/122

    摘要： Administration of human umbilical cord blood cells (HUCBC) or HUCBC-derived plasma is used to treat amyloid-based diseases, such as Alzheimer's disease, Huntington's disease, cerebral amyloid antigopathy, and type-II diabetes. Modulating inflammatory reactions by infusing HUCBC resulted in a marked reduction of amyloid plaques and immune-associated cellular damage. HUCBC infusion also significantly reduced cerebral amyloid angiopathy in mice models. These effects were associated with suppression of the CD40-CD40L interaction and a reduction in surface expressed CD-40 was observed on immune cells. Further, Aβ phagocytic activity was increased and soluble and insoluble Aβ protein levels were modulated by treatment. HUCBC-infused sera also significantly increased phagocytosis of Aβ1-42 peptide and inhibited immune cell CD40 expression and reduced cerebral amyloid angiopathy.

    摘要翻译： 使用人脐带血细胞（HUCBC）或HUCBC衍生血浆来治疗淀粉样蛋白病，如阿尔茨海默氏病，亨廷顿舞蹈病，脑淀粉样蛋白病和II型糖尿病。 通过输注HUCBC调节炎症反应导致淀粉样蛋白斑块和免疫相关细胞损伤的显着减少。 HUCBC输注也显着降低了小鼠模型中的脑淀粉样血管病变。 这些作用与CD40-CD40L相互作用的抑制有关，并且在免疫细胞上观察到表达CD-40的表达减少。 此外，Aβ吞噬活性增加，可溶性和不溶性Aβ蛋白水平通过治疗调节。 HUCBC输注的血清也显着增加了Aβ1-42肽的吞噬作用，抑制了免疫细胞CD40表达，降低了脑淀粉样血管病变。

    Method of prenatal administration of mammalian umbilical cord stem cells for the intrauterine treatment of sanfilippo syndrome
    15.
    发明授权
    Method of prenatal administration of mammalian umbilical cord stem cells for the intrauterine treatment of sanfilippo syndrome 有权
    哺乳动物脐带干细胞产前给药方法，用于子宫内膜治疗Sanfilippo综合征

    公开(公告)号：US09173907B2

    公开(公告)日：2015-11-03

    申请号：US12168608

    申请日：2008-07-07

    申请人： Svitlana Garbuzova-Davis ,  Paul R. Sanberg ,  Sylvia Gografe

    发明人： Svitlana Garbuzova-Davis ,  Paul R. Sanberg ,  Sylvia Gografe

    IPC分类号： A61K35/44

    CPC分类号： A61K35/44

    摘要： A method of treating a fetus or embryo suspected of having a congenital condition that involves an abnormal or missing protein, the method has the steps of a. providing a plurality of human umbilical cord blood in a form suitable for intravenous administration; a b. administering the human umbilical cord blood cells to a mother carrying a fetus of embryo suspected of having said congenital condition. Such congenital conditions include Sanfilippo's syndrome, Hunter's syndrome, Hurler's syndrome, Tay-Sachs disease, Gaucher's disease, von Gierke's disease, Pompes disease, Cori disease, Andersen disease, McArdle's disease, Hers disease, Tauri's disease or Type IX glycogen storage disease.

    摘要翻译： 一种治疗怀疑患有涉及异常或缺失蛋白质的先天性病症的胎儿或胚胎的方法，具有以下步骤：a。 提供适合于静脉内施用形式的多种人脐带血; a b。 对携带怀疑有先天性胚胎的胎儿的母亲施用人脐带血细胞。 这种先天性病症包括Sanfilippo综合征，亨特综合征，赫勒勒综合征，泰萨克病，戈谢病，冯·吉尔克病，庞培病，康利病，安徒生病，麦卡德尔病，赫斯病，牛磺病或1型糖原贮积病。

    METHOD OF TREATING INFLAMMATION USING HUMAN IMMUNOSUPPRESSIVE PROTEIN
    16.
    发明申请
    METHOD OF TREATING INFLAMMATION USING HUMAN IMMUNOSUPPRESSIVE PROTEIN 有权
    使用人体免疫抑制蛋白治疗炎症的方法

    公开(公告)号：US20140234401A1

    公开(公告)日：2014-08-21

    申请号：US14220714

    申请日：2014-03-20

    申请人： Paul R. Sanberg ,  Robert W. Engelman ,  William R. Gower

    发明人： Paul R. Sanberg ,  Robert W. Engelman ,  William R. Gower

    IPC分类号： C07K14/47

    CPC分类号： C07K14/4703 ,  A61K38/00 ,  Y02A50/471

    摘要： A method of treating inflammation by administering a therapeutically effective amount of a human immunosuppressant protein (HISP) to a subject is presented. The inventors have discovered a novel immunosuppressive protein purified from the supernatant of hNT cell culture. The immunosuppressant protein has a molecular weight of about 40-100 kDa, an isoelectric point of about 4.4, a net ionic charge and is capable of suppressing T-cell activation, T-cell proliferation and the production of IL-2. This protein can be used in treating inflammation, preventing graft rejection after transplantation, treating autoimmune diseases and suppressing allergic responses as well as other uses.

    摘要翻译： 提出了通过向受试者施用治疗有效量的人免疫抑制蛋白（HISP）来治疗炎症的方法。 本发明人发现了从hNT细胞培养物的上清液中纯化的新型免疫抑制蛋白。 免疫抑制蛋白具有约40-100kDa的分子量，约4.4的等电点，净离子电荷，并且能够抑制T细胞活化，T细胞增殖和IL-2的产生。 该蛋白质可用于治疗炎症，预防移植后的移植排斥反应，治疗自身免疫疾病和抑制过敏反应以及其他用途。

    CELL THERAPY FOR CHRONIC STROKE
    17.
    发明申请
    CELL THERAPY FOR CHRONIC STROKE 审中-公开
    慢性淋巴细胞疗法

    公开(公告)号：US20140099286A1

    公开(公告)日：2014-04-10

    申请号：US14037990

    申请日：2013-09-26

    申请人： Paul R. Sanberg ,  Douglas Kondziolka ,  Michael P. McGrogan ,  Gary L. Snable

    发明人： Paul R. Sanberg ,  Douglas Kondziolka ,  Michael P. McGrogan ,  Gary L. Snable

    IPC分类号： A61K35/30

    CPC分类号： A61K35/30 ,  A61K48/00

    摘要： A method of treating stroke in a patient who has undergone a stroke comprising administering at least 2 million suitable neuronal cells in at least one brain area involved in the stroke. The method comprises the step of using a twist drill or a burr to form a hole in the skull through which the cells could be administered. Exemplary cells are hNT neuronal cells, HCN-1 cells, fetal pig cells, neural crest cells, neural stem cells, or a combination thereof. Also disclosed herein is a pharmaceutical composition of 95% pure hNT neuronal cells, which composition further includes a vial containing PBS and human neuronal cells. This vial is provided in a container with liquid nitrogen, whereby the composition is frozen and maintained at −170° C. before use. Also disclosed are methods of improving speech, cognitive, sensory, and motor function in a person who has experienced brain damage which interferes with function by administering a sterile composition of a sufficient number of neuronal cells or neural stem cells to the damaged area. Also disclosed is a method of replacing central nervous cells lost to neurodegenerative disease, trauma, ischemia or poisoning.

    摘要翻译： 一种治疗已经发生中风的患者的中风的方法，包括在涉及中风的至少一个脑区域中施用至少200万个合适的神经元细胞。 该方法包括使用麻花钻或毛刺在颅骨中形成可以给予细胞的孔。 示例性细胞是hNT神经元细胞，HCN-1细胞，胎儿猪细胞，神经嵴细胞，神经干细胞或其组合。 本文还公开了95％纯的hNT神经元细胞的药物组合物，该组合物还包括含有PBS和人神经元细胞的小瓶。 将该小瓶设置在具有液氮的容器中，由此在使用前将组合物冷冻并保持在-170℃。 还公开了通过向受损区域施用足够数量的神经元细胞或神经干细胞的无菌组合物来改善经历脑功能损害的人的语言，认知，感觉和运动功能的方法。 还公开了一种替代神经变性疾病，创伤，缺血或中毒损失的中枢神经细胞的方法。