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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS048349-04
Application #
7341707
Study Section
Clinical Neuroscience and Disease Study Section (CND)
Program Officer
Golanov, Eugene V
Project Start
2004-12-01
Project End
2009-11-30
Budget Start
2007-12-01
Budget End
2008-11-30
Support Year
4
Fiscal Year
2008
Total Cost
$327,034
Indirect Cost
Name
Henry Ford Health System
Department
Neurology
Type
Schools of Medicine
DUNS #
073134603
City
Detroit
State
MI
Country
United States
Zip Code
48202
Jiang, Quan (2016) Magnetic resonance imaging and cell-based neurorestorative therapy after brain injury. Neural Regen Res 11:7-14
Ding, Guang-Liang; Chopp, Michael; Li, Lian et al. (2014) Magnetic Resonance Imaging of Stroke in the Rat. Bo Pu Xue Za Zhi 31:116-132
Wang, Shiyang; Chopp, Michael; Nazem-Zadeh, Mohammad-Reza et al. (2013) Comparison of neurite density measured by MRI and histology after TBI. PLoS One 8:e63511
Li, Lian; Chopp, Michael; Ding, Guang Liang et al. (2012) MRI measurement of angiogenesis and the therapeutic effect of acute marrow stromal cell administration on traumatic brain injury. J Cereb Blood Flow Metab 32:2023-32
Jiang, Quan; Thiffault, Christine; Kramer, Brian C et al. (2012) MRI detects brain reorganization after human umbilical tissue-derived cells (hUTC) treatment of stroke in rat. PLoS One 7:e42845
Jiang, Quan; Ewing, James R; Chopp, Michael (2012) MRI of blood-brain barrier permeability in cerebral ischemia. Transl Stroke Res 3:56-64
Varma, Nadimpalli Ravi S; Janic, Branislava; Iskander, A S M et al. (2012) Endothelial progenitor cells (EPCs) as gene carrier system for rat model of human glioma. PLoS One 7:e30310
Ding, Guangliang; Jiang, Quan; Li, Lian et al. (2011) Longitudinal magnetic resonance imaging of sildenafil treatment of embolic stroke in aged rats. Stroke 42:3537-41
Bosomtwi, Asamoah; Chopp, Michael; Zhang, Li et al. (2011) Mean microvessel segment length and radius after embolic stroke: Comparison of magnetic resonance imaging (MRI) and laser scanning confocal microscopy (LSCM). Brain Res 1381:217-27
Jiang, Quan; Qu, Changsheng; Chopp, Michael et al. (2011) MRI evaluation of axonal reorganization after bone marrow stromal cell treatment of traumatic brain injury. NMR Biomed 24:1119-28

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