title: Transplantation of marrow stromal cells restores cerebral blood flow and reduces cerebral atrophy in rats with traumatic brain injury: in vivo MRI study.
abstract: 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 × 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.
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, Michigan 48202, USA.
authors.forename: Lian
authors.initials: L
authors.lastname: Li
authors.forename: Quan
authors.initials: Q
authors.lastname: Jiang
authors.forename: Chang Sheng
authors.initials: CS
authors.lastname: Qu
authors.forename: Guang Liang
authors.initials: GL
authors.lastname: Ding
authors.forename: Qing Jiang
authors.initials: QJ
authors.lastname: Li
authors.forename: Shi Yang
authors.initials: SY
authors.lastname: Wang
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.forename: Asim
authors.initials: A
authors.lastname: Mahmood
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000818:Animals; D001284:Atrophy / Q000473:pathology / Q000628:therapy*; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D001921:Brain / Q000473:pathology*; D001930:Brain Injuries / Q000473:pathology / Q000628:therapy*; D002560:Cerebrovascular Circulation; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017154:Stromal Cells / Q000637:transplantation