Vascularized perfused microtissue/micro-organ arrays
    2.
    发明授权
    Vascularized perfused microtissue/micro-organ arrays 有权
    血管灌注微组织/微器官阵列

    公开(公告)号:US06197575B1

    公开(公告)日:2001-03-06

    申请号:US09272227

    申请日:1999-03-18

    IPC分类号: C12M134

    摘要: Systems including (1) a micromatrix and perfusion assembly suitable for seeding and attachment of cells within the matrix and for morphogenesis of seeded cells into complex, hierarchical tissue or organ structures, wherein the matrix includes channels or vessels through which culture medium, oxygen, or other nutrient or body fluids can be perfused while controlling gradients of nutrients and exogenous metabolites throughout the perfusion path independently of perfusion rate, and (2) sensor means for detecting changes in either cells within the matrix or in materials exposed to the cells, have been developed. Methods for making the micromatrices include micromachining, micromolding, embossing, laser drilling, and electro deposition machining. Cells can be of one or more types, either differentiated or undifferentiated. In a preferred embodiment, the matrix is seeded with a mixture of cells including endothelial cells which will line the channels to form “blood vessels”, and at least one type of parenchymal cells, such as hepatocytes, pancreatic cells, or other organ cells. The system can be used to screen materials for an effect on the cells, for an effect of the cells on the materials (for example, in a manner equivalent to tissue metabolism of a drug), or to test a material on a biological that must first infect cells or tissues, such as viruses. The apparatus also can be used to provide a physiological environment for expansion of stem cells, or for enabling gene therapy in vitro.

    摘要翻译: 系统包括(1)微阵列和灌注组件,其适合于接种和附着基质内的细胞,并将种子细胞的形态发生转化为复杂的分层组织或器官结构,其中所述基质包括通道或血管,培养基,氧气或 可以灌注其他营养液或体液,同时在整个灌注路径中独立于灌注速率控制营养物质和外源代谢物的梯度,以及(2)用于检测基质内的任何细胞或暴露于细胞的材料中的变化的传感器装置, 发达。 制造微阵列的方法包括微加工,微型成型,压花,激光钻孔和电沉积加工。 细胞可以是一种或多种,​​分化或未分化。 在优选的实施方案中,用包含内皮细胞的细胞混合物接种基质,所述内皮细胞将通道形成“血管”,以及至少一种类型的实质细胞,例如肝细胞,胰腺细胞或其它器官细胞。 该系统可以用于筛选对细胞的影响的材料,用于细胞对材料的影响(例如,以与药物的组织代谢相当的方式),或测试生物上必需的材料 首先感染细胞或组织,如病毒。 该装置还可用于提供用于扩大干细胞的生理环境,或用于在体外实现基因治疗。

    Compositions of and methods of using ligand dimers
    5.
    发明授权
    Compositions of and methods of using ligand dimers 有权
    使用配体二聚体的组成和方法

    公开(公告)号:US09198952B2

    公开(公告)日:2015-12-01

    申请号:US13120184

    申请日:2009-09-22

    摘要: Provided herein are ligand dimers, compositions thereof, as well as methods of their use. The ligand dimers provided can comprise at least one ligand to a Her receptor and can be used to force dimerization of specific receptor pairs. The forced dimerization of specific receptor pairs can be used to control (e.g., promote or inhibit) signaling, and, therefore, the ligand dimers provided can also be used in various forms of treatment in which such signaling control is beneficial to a subject. It follows that methods for controlling signaling are provided as are various methods of treatment.

    摘要翻译: 本文提供了配体二聚体,其组合物,以及它们的使用方法。 所提供的配体二聚体可以包含至少一种Her受体的配体,并可用于强制特异性受体对的二聚化。 特异性受体对的强制二聚可用于控制(例如,促进或抑制)信号传导,因此,所提供的配体二聚体也可用于各种形式的治疗,其中这种信号传导控制对受试者有益。 因此,提供用于控制信号传导的方法是各种治疗方法。

    Porous biodegradable polymeric materials for cell transplantation
    6.
    发明授权
    Porous biodegradable polymeric materials for cell transplantation 失效
    用于细胞移植的多孔可生物降解聚合物材料

    公开(公告)号:US07462471B2

    公开(公告)日:2008-12-09

    申请号:US10775768

    申请日:2004-02-10

    摘要: Polymeric materials are used to make a pliable, non-toxic, injectable porous template for vascular ingrowth. The pore size, usually between approximately 100 and 300 microns, allows vascular and connective tissue ingrowth throughout approximately 10 to 90% of the matrix following implantation, and the injection of cells uniformly throughout the implanted matrix without damage to the cells or patient. The introduced cells attach to the connective tissue within the matrix and are fed by the blood vessels. The preferred material for forming the matrix or support structure is a biocompatible synthetic polymer which degrades in a controlled manner by hydrolysis into harmless metabolites, for example, polyglycolic acid, polylactic acid, polyorthoester, polyanhydride, or copolymers thereof. The rate of tissue ingrowth increases as the porosity and/or the pore size of the implanted devices increases. The time required for the tissue to fill the device depends on the polymer crystallinity and is less for amorphous polymers versus semicrystalline polymers. The vascularity of the advancing tissue is consistent with time and independent of the biomaterial composition and morphology.

    摘要翻译: 聚合材料用于制造一种柔韧,无毒,可注射的多孔模板,用于血管向内生长。 通常在约100和300微米之间的孔径允许血管和结缔组织在植入后约10至90%的基质向内生长,并且在整个植入的基质中均匀注射细胞而不损伤细胞或患者。 引入的细胞附着到基质内的结缔组织,并由血管进食。 用于形成基质或支撑结构的优选材料是生物相容的合成聚合物,其通过水解以受控的方式降解成无害的代谢物,例如聚乙醇酸,聚乳酸,聚原酸酯,聚酐或其共聚物。 随着植入装置的孔隙率和/或孔径增加,组织向内生长的速率增加。 组织填充装置所需的时间取决于聚合物的结晶度,对于无定形聚合物与半结晶聚合物相比较少。 前进组织的血管分布与时间一致,与生物材料组成和形态无关。

    METHODS AND COMPOSITIONS FOR CARDIOPROTECTION AND CARDIOREGENERATION
    10.
    发明申请
    METHODS AND COMPOSITIONS FOR CARDIOPROTECTION AND CARDIOREGENERATION 有权
    心脏保护和心脏发育的方法和组合物

    公开(公告)号:US20130196911A1

    公开(公告)日:2013-08-01

    申请号:US13636578

    申请日:2011-03-24

    IPC分类号: A61K38/18

    摘要: The invention provides methods and compositions for reducing, preventing or reversing cardio toxicity side effects associated with certain therapeutic agents. The invention also provides methods and compositions for treating heart dysfunction including heart failure, and for reversing the effects of myocardial infarction. The various aspects of the invention involve the use of ligand dimers, such as neuregulin dimers, that selectively induce the dimerization of certain EGF receptors in cardiac tissue.

    摘要翻译: 本发明提供用于减少,预防或逆转与某些治疗剂相关的心脏毒性副作用的方法和组合物。 本发明还提供了用于治疗包括心力衰竭的心脏功能障碍以及用于逆转心肌梗塞的作用的方法和组合物。 本发明的各个方面涉及使用选择性诱导心脏组织中某些EGF受体的二聚化的配体二聚体,例如神经调节蛋白二聚体。