title: Effects of administration route on migration and distribution of neural progenitor cells transplanted into rats with focal cerebral ischemia, an MRI study.
abstract: We tested the hypotheses that administration routes affect the migration and distribution of grafted neural progenitor cells (NPCs) in the ischemic brain and that the ischemic lesion plays a role in mediating the grafting process. Male Wistar rats (n=41) were subjected to 2-h middle cerebral artery occlusion (MCAo), followed 1 day later by administration of magnetically labeled NPCs. Rats with MCAo were assigned to one of three treatment groups targeted for cell transplantation intra-arterially (IA), intracisternally (IC), or intravenously (IV). MRI measurements consisting of T2-weighted imaging and three-dimensional (3D) gradient echo imaging were performed 24 h after MCAo, 4 h after cell injection, and once a day for 4 days. Prussian blue staining was used to identify the labeled cells, 3D MRI to detect cell migration and distribution, and T2 map to assess lesion volumes. Intra-arterial (IA) administration showed significantly increased migration, a far more diffuse distribution pattern, and a larger number of transplanted NPCs in the target brain than IC or IV administration. However, high mortality with IA delivery (IA: 41%; IC: 17%; IV: 8%) poses a serious concern for using this route of administration. Animals with smaller lesions at the time of transplantation have fewer grafted cells in the parenchyma.
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: Guangliang
authors.initials: G
authors.lastname: Ding
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Zheng Gang
authors.initials: ZG
authors.lastname: Zhang
authors.forename: Qingjiang
authors.initials: Q
authors.lastname: Li
authors.forename: Swayamprava
authors.initials: S
authors.lastname: Panda
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.forename: James R
authors.initials: JR
authors.lastname: Ewing
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D002465:Cell Movement / Q000502:physiology*; D002946:Cisterna Magna; D007091:Image Processing, Computer-Assisted; D007267:Injections; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D009474:Neurons / Q000637:transplantation*; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D016707:Tissue Fixation