Transplantation of Marrow Stromal Cells Restores Cerebral Blood Flow and Reduces Cerebral Atrophy in Rats with Traumatic Brain Injury: In vivo MRI Study

被引:34
作者
Li, Lian [1 ]
Jiang, Quan [1 ]
Qu, Chang Sheng [2 ]
Ding, Guang Liang [1 ]
Li, Qing Jiang [1 ]
Wang, Shi Yang [4 ]
Lee, Ji Hyun [4 ]
Lu, Mei [3 ]
Mahmood, Asim [2 ]
Chopp, Michael [1 ]
机构
[1] Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA
[2] Henry Ford Hosp, Dept Neurosurg, Detroit, MI 48202 USA
[3] Henry Ford Hosp, Dept Biostat & Res Epidemiol, Detroit, MI 48202 USA
[4] Oakland Univ, Dept Phys, Rochester, MI USA
关键词
cerebral atrophy; cerebral blood flow; marrow stromal cells; MRI; ventricular expansion; VOLUME; MODERATE; MILD; PERFUSION; ISCHEMIA; DAMAGE; DEATH;
D O I
10.1089/neu.2010.1619
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Cell therapy promotes brain remodeling and improves functional recovery after various central nervous system disorders, including traumatic brain injury (TBI). We tested the hypothesis that treatment of TBI with intravenous administration of human marrow stromal cells (hMSCs) provides therapeutic benefit in modifying hemodynamic and structural abnormalities, which are detectable by in vivo MRI. hMSCs were labeled with superparamagnetic iron oxide (SPIO) nanoparticles. Male Wistar rats (300-350 g, n = 18) subjected to controlled cortical impact TBI were intravenously injected with 1 mL of saline (n = 9) or hMSCs in suspension (n = 9, approximately 3 x 10(6) SPIO-labeled hMSCs) 5 days post-TBI. In vivo MRI measurements consisting of cerebral blood flow (CBF), T2-weighted imaging, and 3D gradient echo imaging were performed for all animals 2 days post-TBI and weekly for 6 weeks. Functional outcome was evaluated with modified neurological severity score and Morris water maze test. Cell engraftment was detected in vivo by 3D MRI and confirmed by double staining. Ventricle and lesion volumetric alterations were measured using T2 maps, and hemodynamic abnormality was tracked by MRI CBF measurements. Our data demonstrate that treatment with hMSCs following TBI diminishes hemodynamic abnormalities by early restoration and preservation of CBF in the brain regions adjacent to and remote from the impact site, and reduces generalized cerebral atrophy, all of which may contribute to the observed improvement of functional outcome.
引用
收藏
页码:535 / 545
页数:11
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