In vivo MR Evaluation of Cell Therapy for Stroke

中风细胞疗法的体内 MR 评估

• 批准号: 6871428
• 负责人: QUAN JIANG
• 金额: $ 31.56万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6871428
• 关键词: angiogenesis; behavior test; bioimaging /biomedical imaging; bone marrow; brain cell; brain circulation; brain imaging /visualization /scanning; cell cell interaction; cell migration; cell transplantation; confocal scanning microscopy; contrast media; functional ability; functional magnetic resonance imaging; immunocytochemistry; laboratory rat; magnetic field; magnetic resonance imaging; nonhuman therapy evaluation; stroke; stroke therapy; stromal cells; technology /technique development; therapy design /development; three dimensional imaging /topography

DESCRIPTION (provided by applicant): Treatment of stroke with bone marrow stromal cells (MSCs) significantly improves functional recovery in experimental stroke. However, little is known about temporal and spatial profiles of migration of transplanted MSCs and the effects of these cells on host cerebral tissue leading to functional recovery. We propose to develop noninvasive in vivo magnetic resonance (MR) methodology for tracking transplanted MSCs and investigating their effects on the host brain. In Specific Aim 1, we will first optimize methodology for magnetic contrast agent labeling and in vivo three dimensional magnetic resonance (MRI) monitoring of transplanted MSCs in the host brain. Using the optimized methodology, we will then examine the effects of different routes (intravenous vs intracisternal) of transplantation on survival, migration, and distribution patterns of transplanted cells in brain subjected to stroke. In Specific Aim 2, dynamic effects of transplanted MSCs on the host brain angiogenesis and functional recovery after stroke will be noninvasively measured by means of MR. Neurological outcome will be measured using a battery of behavioral tests. Correlation between changes in MR measurements and dynamic functional improvements will be analyzed in the same animal. In addition, changes in MR measurements of angiogenesis resulting from MSC transplantation will be verified using three dimensional laser scanning confocal microscopy in combination with immuno-histochemistry. With these novel approaches, we expect that noninvasive MR measurements will simultaneously detect the migration and distribution of transplanted cells and the effects of these cells on the host brain tissue, and that changes in MR measurements will correlate to neurological function. Therefore, MR could potentially provide important noninvasive measurements for developing a successful cell therapy for stroke. After completing our studies, we expect to demonstrate that MR tracking magnetic labeled cells is a valid new technique for studying cell therapy for stroke, which will lead to optimization of cell transplantation protocols and improved management of stroke.

描述（由申请人提供）：用骨髓基质细胞（MSC）治疗中风可显着改善实验性中风的功能恢复。然而，对于移植的间充质干细胞迁移的时间和空间分布以及这些细胞对宿主脑组织导致功能恢复的影响知之甚少。我们建议开发无创体内磁共振（MR）方法来跟踪移植的间充质干细胞并研究它们对宿主大脑的影响。在具体目标 1 中，我们将首先优化磁性造影剂标记和宿主大脑中移植 MSC 的体内三维磁共振 (MRI) 监测的方法。然后，我们将使用优化的方法来检查不同移植途径（静脉内与脑池内）对中风大脑中移植细胞的存活、迁移和分布模式的影响。在具体目标2中，将通过MR无创测量移植的间充质干细胞对宿主脑血管生成和中风后功能恢复的动态影响。神经学结果将通过一系列行为测试来测量。将在同一动物中分析 MR 测量变化和动态功能改善之间的相关性。此外，MSC 移植引起的血管生成的 MR 测量变化将使用三维激光扫描共聚焦显微镜结合免疫组织化学进行验证。通过这些新方法，我们预计无创 MR 测量将同时检测移植细胞的迁移和分布以及这些细胞对宿主脑组织的影响，并且 MR 测量的变化将与神经功能相关。因此，MR 可能为开发成功的中风细胞疗法提供重要的无创测量。完成研究后，我们希望证明 MR 跟踪磁性标记细胞是研究中风细胞疗法的有效新技术，这将导致细胞移植方案的优化和中风治疗的改善。