Migration of Human Neural Stem Cells In Vitro and In Vivo

人类神经干细胞的体外和体内迁移

• 批准号: 7907627
• 负责人: ALFREDO QUINONES-HINOJOSA
• 金额: $ 17.61万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7907627
• 关键词: Adult; Astrocytes; Astrocytoma; Autopsy; Behavior; Biological Assay; Biology; Brain; Brain Neoplasms; Cells; Development; Disease; Electron Microscopy; Ependyma; Epidermal Growth Factor; Epidermal Growth Factor Receptor; Glioblastoma; Glioma; Goals; Growth; Harvest; Human; In Vitro; Lead; Location; Malignant Glioma; Malignant neoplasm of brain; Microscopy; Migration Assay; Modeling; Neuroglia; Neurons; Patients; Population; Primary Neoplasm; Process; Public Health; Quinones; Receptor Activation; Research Personnel; Rodent; Rodent Model; Role; Source; Specimen; Spottings; Stem cells; Time; Tumor Cell Invasion; cancer cell; cancer stem cell; cell motility; fetal; fetal stem cell; human adult stem cell; human migration; human stem cells; human tissue; immunocytochemistry; in vivo; insight; matrigel; migration; nerve stem cell; programs; repaired; subventricular zone; tumor

DESCRIPTION (provided by applicant): The subventricular zone (SVZ) has been shown to be the largest germinal region in the adult rodent brain. Recent studies have also demonstrated not only that a similar neurogenic region exists in the SVZ of the adult human brain, but also that the cytoarchitecture is different in the human SVZ: a hypocellular gap and a ribbon of astrocytes is present under the ependyma. It remains unknown whether neural stem cells in the human brain are precisely localized in this ribbon of astrocytes lining the adult human SVZ and whether these adult neural stem cells have the ability to migrate. What exactly regulates the migratory capacity of stem cells or the transformation of brain tumors is not known, but epidermal growth factor (EOF) has been implicated in this process. Within this context we will pursue the following Specific Aims: Aim 1: To precisely localize the adult human neural stem cells with respect to the ependyma and to compare the adult human SVZ to the fetal human SVZ and to the SVZ of patients with gliomas. The hypothesis is that stem cells are concentrated in the band of astrocytes parallel to the ependyma and that this ribbon of astrocytes is 1) more prominent when patients have gliomas that are adjacent and/or part of the subventricular zone; 2) there is a larger population of CD 133+cells within this ribbon of astrocytes in patients with brain tumors 3) this ribbon of astrocytes does not exist in the fetal human SVZ. Aim 2: To establish the role of EGF in the migratory ability of adult, fetal, and human brain cancer stem cells using both in vitro migration assays and an in vivo rodent model. The hypothesis is that human adult stem cells have the ability to migrate and that their manipulation with EGF can change them to a more aggressive migratory behavior that resembles that of the fetal human brain and/or high grade tumors. This project has direct relevance to public health. If adult neural stem cells have the ability to migrate we will further elucidate the human brain's capacity for self-repair and may be able to figure out ways to make these cells migrate to replace those lost following extensive neuronal damage or disease. In addition, neural stem cells and cancer stem cells may share similar mechanisms of migration and invasion and understanding this mechanism may lead to better treatments of brain tumors.

描述（由申请人提供）：室内区（SVZ）已被证明是成年啮齿动物大脑中最大的生发区域。最近的研究还表明，不仅在成年人脑的SVZ中存在类似的神经源区域，而且在人类SVZ中的细胞结构也有所不同：小细胞间隙和e宿主体下存在的星形胶质细胞。尚不清楚人脑中的神经干细胞是否精确地定位在成年人类SVZ的星形胶质细胞中，以及这些成年神经干细胞是否具有迁移的能力。确切地调节干细胞迁移能力或脑肿瘤的转化是什么，而表皮生长因子（EOF）已与此过程有关。在这种情况下，我们将追求以下特定目的：目标1：准确地将成年人类神经干细胞相对于de膜室，并将成年人的人类SVZ与胎儿人类SVZ进行比较，并将神经胶质瘤患者的SVZ进行比较。假设是，干细胞集中在平行于dend症的星形胶质细胞带中，而这种星形胶质细胞的丝带更为突出，当患者的神经胶质瘤邻近和/或一部分是脑动脉膜下区域； 2）在这种星形胶质细胞中，脑肿瘤患者的CD 133+细胞群较大。3）胎儿人类SVZ中不存在这种星形胶质细胞的色带。目标2：使用体外迁移测定和体内啮齿动物模型，确定EGF在成人，胎儿和人脑癌干细胞的迁移能力中的作用。假设是人类的成年干细胞具有迁移的能力，并且它们用EGF的操纵可以将它们变成更具侵略性的迁移行为，类似于胎儿人脑和/或高级肿瘤的迁移行为。该项目与公共卫生有直接相关。如果成年神经干细胞具有迁移的能力，我们将进一步阐明人脑的自我修复能力，并可能能够找出使这些细胞迁移以取代那些在广泛的神经元损害或疾病后丧失的人的方法。此外，神经干细胞和癌症干细胞可能具有相似的迁移和侵袭机制，并且理解这种机制可能会导致更好地治疗脑肿瘤。

项目成果

Responses of glial cells to stress and glucocorticoids.

• DOI: 10.2174/157339510791823790
• 发表时间: 2010-08-01
• 期刊: Current immunology reviews
• 作者: Jauregui-Huerta F;Ruvalcaba-Delgadillo Y;Gonzalez-Castañeda R;Garcia-Estrada J;Gonzalez-Perez O;Luquin S
• 通讯作者: Luquin S

Neurosphere culture and human organotypic model to evaluate brain tumor stem cells.

• DOI: 10.1007/978-1-59745-280-9_6
• 发表时间: 2009
• 期刊: Methods in molecular biology (Clifton, N.J.)

Regulation of brain tumor dispersal by NKCC1 through a novel role in focal adhesion regulation.

• DOI: 10.1371/journal.pbio.1001320
• 发表时间: 2012
• 期刊: PLoS biology
• 影响因子: 9.8
• 作者: Garzon-Muvdi T;Schiapparelli P;ap Rhys C;Guerrero-Cazares H;Smith C;Kim DH;Kone L;Farber H;Lee DY;An SS;Levchenko A;Quiñones-Hinojosa A
• 通讯作者: Quiñones-Hinojosa A

Immunological regulation of the central nervous system: From physiological to pathological processes.

中枢神经系统的免疫调节：从生理到病理过程。

• DOI: 10.2174/157339510791823736
• 发表时间: 2010
• 期刊: Current immunology reviews
• 作者: Gonzalez-Perez,Oscar

Gliomagenesis and the use of neural stem cells in brain tumor treatment.

• DOI: 10.2174/187152010790909290
• 发表时间: 2010-02
• 期刊: Anti-cancer agents in medicinal chemistry
• 影响因子: 2.8
• 作者: Achanta P;Sedora Roman NI;Quiñones-Hinojosa A
• 通讯作者: Quiñones-Hinojosa A