Method of stem cell delivery into the brain during chronic disease using blood brain barrier permeabilizers

    公开(公告)号:US10765706B2

    公开(公告)日:2020-09-08

    申请号:US15257315

    申请日:2016-09-06

    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.

    Combination therapy of stem cell mobilizing agents and stem cell transplantation

    公开(公告)号:US10130683B1

    公开(公告)日:2018-11-20

    申请号:US14823637

    申请日:2015-08-11

    IPC分类号: A61K35/51 A61K38/19 A61K9/00

    摘要: A combined therapy of human umbilical cord blood cells (hUCB) and G-CSF at the acute stage of TBI was tested as a therapeutic for progressive secondary effects of chronic TBI. Rats were treated with saline carrier, or therapeutic in carrier as follows; G-CSF, hUCB, or hUCB and G-CSF, 7-days after TBI. Eight weeks later, behavioral testing was performed and brains harvested to analyze hippocampal cell loss, neuroinflammatory response, and neurogenesis. Results revealed that the monotherapies partially suppressed neuroinflammation and reduced hippocampal cell loss. However, combined therapy of hUCB and G-CSF robustly dampened neuroinflammation, while enhancing endogenous neurogenesis and reducing hippocampal cell loss. Vigorous and long-lasting recovery of motor function accompanied the combined therapy, which was either moderately or short-lived in the monotherapy conditions. These results suggest that combined treatment rather than monotherapy appears optimal for abrogating histophalogical and motor impairments in chronic TBI.

    METHOD OF STEM CELL DELIVERY INTO THE BRAIN DURING CHRONIC DISEASE USING BLOOD BRAIN BARRIER PERMEABILIZERS
    3.
    发明申请
    METHOD OF STEM CELL DELIVERY INTO THE BRAIN DURING CHRONIC DISEASE USING BLOOD BRAIN BARRIER PERMEABILIZERS 审中-公开
    使用血脑膜阻滞剂治疗慢性疾病的干细胞移植到脑中的方法

    公开(公告)号:US20170065643A1

    公开(公告)日:2017-03-09

    申请号:US15257315

    申请日:2016-09-06

    IPC分类号: A61K35/51 A61K47/26

    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.

    摘要翻译: 血脑屏障(BBB)渗透剂如甘露醇可以促进干细胞从外周进入脑卒中。 在慢性疾病阶段BBB渗透是否还有助于干细胞从外周进入受损脑。 本文的证据表明,BBB在慢性中风期的渗透有助于干细胞从外周进入脑卒中。 仅用人脐带干细胞(hUCBC)处理的中风模型(200万活细胞),甘露醇或组合。 结果显示,与对照动物相比,hUCBC单独或与甘露醇组合显示出显着的行为和组织学缺陷,HUCBC-甘露醇联合治疗显示出在脑梗死区域的脑细胞存活中仅用于hUCBC治疗的改善。 慢性脑卒中中的BBB渗透也降低了改善功能结果所需的有效干细胞剂量。

    Methods of treating stroke using stem cell-like menstrual blood cells
    5.
    发明授权
    Methods of treating stroke using stem cell-like menstrual blood cells 有权
    使用干细胞样月经血细胞治疗中风的方法

    公开(公告)号:US09044431B2

    公开(公告)日:2015-06-02

    申请号:US13107391

    申请日:2011-05-13

    IPC分类号: A61K35/30 A61K35/14 A61K38/18

    摘要: A cell type that is a complete match of the transplant recipient appears as an optimal scenario to open treatment options to a large patient population with minimal complications. The use of autologous bone marrow or umbilical cord blood has been proposed as a good source of stem cells for cell therapy. Menstrual blood is found to be another important source of stem cells. Assays of cultured menstrual blood reveal that they express embryonic like-stem cell phenotypic markers and neuronal phenotypic markers under appropriate conditioned media. Oxygen glucose deprivation stroke models show that OGD-exposed primary rat neurons, co-cultured with menstrual blood-derived stem cells or exposed to the media from cultured menstrual blood, exhibited significantly reduced cell death. Transplantation of menstrual blood-derived stem cells, either intracerebrally or intravenously, after experimentally induced ischemic stroke in adult rats also significantly reduced behavioral and histological impairments compared to vehicle-infused rats.

    摘要翻译: 与移植受体完全匹配的细胞类型似乎是最佳方案,以最小的并发症向大量患者群体开放治疗选择。 已经提出使用自体骨髓或脐带血作为细胞治疗的干细胞的良好来源。 月经血被认为是干细胞的另一个重要来源。 培养的月经血液的测定显示它们在合适的条件培养基下表达胚胎样干细胞表型标记物和神经元表型标记物。 氧葡萄糖剥夺中风模型显示,OGD暴露的原代大鼠神经元,与月经血源干细胞共培养或暴露于来自培养的月经血液的培养基,显示出显着降低的细胞死亡。 在实验性诱导的成年大鼠缺血性卒中后,月经血液或静脉内移植月经血源性干细胞也显着降低与载体输注大鼠相比的行为和组织学损伤。

    Human immunosuppressive protein
    6.
    发明授权
    Human immunosuppressive protein 有权
    人免疫抑制蛋白

    公开(公告)号:US08716216B2

    公开(公告)日:2014-05-06

    申请号:US12118675

    申请日:2008-05-09

    IPC分类号: A61K38/00 C07K14/47 C07K14/55

    摘要: A composition of an immunosuppressant protein (HISP) which is achieved by the steps of obtaining supernatant from hNT neuronal cells; exposing the supernatant to preparative polyacrylamide gel; placing the active isoelectric fraction on a Blue Sepharose column to bind albumin; and collecting the free fraction containing the concentrated, isolated HISP. The HISP is anionic, has a molecular weight of 40-100 kDa, an isoelectric point of about 4.8 and is obtained from the supernatant of hNT cells. HISP can suppress proliferation of responder peripheral blood mononuclear cells in allogeneic mixed lymphocyte cultures; HISP can suppress T-cell proliferation and IL-2 production in response to phorbol 12-myristate 13-acetate (PMA), ionomycin and concanavalin-A. HISP does not act through the T-cell receptor-CD3 complex or via altered accessory signal cells.

    摘要翻译: 通过从hNT神经元细胞获得上清液的步骤实现的免疫抑制蛋白(HISP)的组合物; 将上清液暴露于制备型聚丙烯酰胺凝胶; 将活性等电点部分置于蓝色琼脂糖凝胶柱上以结合白蛋白; 并收集含有浓缩,分离的HISP的游离级分。 HISP为阴离子型,分子量为40-100kDa,等电点为约4.8,由hNT细胞的上清液得到。 HISP可以抑制同种异体混合淋巴细胞培养物中应答者外周血单核细胞的增殖; HISP可以抑制佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA),离子霉素和伴刀豆素A的T细胞增殖和IL-2产生。 HISP不通过T细胞受体-CD3复合物或通过改变的附属信号细胞起作用。

    PROLIFERATED CELL LINES AND USES THEREOF
    7.
    发明申请
    PROLIFERATED CELL LINES AND USES THEREOF 有权
    增殖细胞系及其用途

    公开(公告)号:US20120148540A1

    公开(公告)日:2012-06-14

    申请号:US13267346

    申请日:2011-10-06

    IPC分类号: A61K35/12 C12N5/071

    摘要: The subject invention pertains to tumor cell lines useful for increasing the proliferation potential of any human or animal cell in culture, thereby providing immortalized or continuous cell lines and cultures. The invention also concerns proliferation factors, and compositions containing the factors, which are capable of increasing the proliferation potential of any human or other animal cell in culture. The subject invention further pertains to a method for proliferating cells in culture by contacting cells with the proliferation factors. The proliferated cells can range in plasticity and can include, for example, blast cells, fertilized ova, non-fertilized gametes, embryonic stem cells, adult stem cells, precursor or progenitor cells, and highly specialized cells. Optionally, the cells can be induced to cease proliferation. The proliferated cells of the subject invention are useful for cell therapy, cell/gene therapy, biological production of molecules, and as in vitro models for research, toxicity testing, and drug development.

    摘要翻译: 本发明涉及可用于增加培养物中任何人或动物细胞的增殖潜力的肿瘤细胞系,从而提供永生化或连续的细胞系和培养物。 本发明还涉及增殖因子和含有因子的组合物,其能够增加培养物中任何人或其他动物细胞的增殖潜力。 本发明还涉及通过使细胞与增殖因子接触来增殖培养细胞的方法。 增殖的细胞可以在可塑性范围内,并且可以包括例如胚细胞,受精卵,非受精配子,胚胎干细胞,成体干细胞,前体或祖细胞和高度专门的细胞。 任选地,可诱导细胞停止增殖。 本发明的增殖细胞可用于细胞治疗,细胞/基因治疗,分子的生物制备,以及用于研究,毒性测试和药物开发的体外模型。

    NOVEL METHOD OF PRENATAL ADMINISTRATION OF MAMMALIAN UMBILICAL CORD STEM CELLS FOR THE INTRAUTERINE TREATMENT OF MAMMALIAN LYSOSOMAL STORAGE DISEASES
    8.
    发明申请
    NOVEL METHOD OF PRENATAL ADMINISTRATION OF MAMMALIAN UMBILICAL CORD STEM CELLS FOR THE INTRAUTERINE TREATMENT OF MAMMALIAN LYSOSOMAL STORAGE DISEASES 有权
    用于治疗MAMMALIAN LYSOSOMAL存储疾病的MAMMALIAN脐带干细胞的初步施用方法

    公开(公告)号:US20090016998A1

    公开(公告)日:2009-01-15

    申请号:US12168608

    申请日:2008-07-07

    IPC分类号: A61K35/12 A61P43/00

    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。

    Sertoli cells as biochambers
    9.
    发明授权
    Sertoli cells as biochambers 失效
    Sertoli细胞作为生物体

    公开(公告)号:US06790441B1

    公开(公告)日:2004-09-14

    申请号:US09593629

    申请日:2000-06-13

    IPC分类号: A01N6500

    摘要: According to the present invention, there is provided a biological chamber system having a biochamber defined by outer walls of Sertoli cells. Also provided is a transplantation facilitator including a biochamber. A method of making biochambers by co-culturing facilitator cells and therapeutic cells and then aggregating the facilitator celes is also provided. Also provided is a method of transplanting cells by incorporating transplant cells into a biochamber and transplanting the biochamber containing the transplant cells.

    摘要翻译: 根据本发明,提供了一种具有由Sertoli细胞的外壁限定的生物室的生物室系统。 还提供了包括生物室的移植促进剂。 还提供了通过共培养促进细胞和治疗细胞然后聚集辅助细胞来制备生物体的方法。 还提供了通过将移植细胞并入生物室并移植含有移植细胞的生物室来移植细胞的方法。