In vivo MR Evaluation of Cell Therapy for Stroke

描述（由申请人提供）：用骨髓基质细胞（MSC）治疗中风显著改善实验性中风的功能恢复。然而，很少有人知道的时间和空间分布迁移的移植间充质干细胞和这些细胞对宿主脑组织的影响，导致功能恢复。我们建议开发非侵入性的体内磁共振（MR）的方法来跟踪移植的MSCs，并调查其对宿主脑的影响。在具体目标1中，我们将首先优化用于磁造影剂标记和在宿主脑中移植的MSC的体内三维磁共振（MRI）监测的方法。使用优化的方法，我们将研究不同途径（静脉内与脑池内）移植对中风脑内移植细胞存活、迁移和分布模式的影响。在特定目标2中，移植的MSC对宿主脑血管生成和中风后功能恢复的动态影响将通过MR非侵入性地测量。神经学结果将使用一系列行为测试来测量。将在同一只动物中分析MR测量值变化与动态功能改善之间的相关性。此外，将使用三维激光扫描共聚焦显微镜结合免疫组织化学来验证MSC移植引起的血管生成的MR测量的变化。通过这些新方法，我们期望非侵入性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非侵入性测量。在完成我们的研究后，我们希望证明MR跟踪磁标记细胞是研究中风细胞治疗的有效新技术，这将导致细胞移植方案的优化和中风管理的改善。

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.