Original Article

Journal of Cerebral Blood Flow & Metabolism advance online publication 4 November 2009; doi: 10.1038/jcbfm.2009.238

Effects of administration route on migration and distribution of neural progenitor cells transplanted into rats with focal cerebral ischemia, an MRI study

This work was supported by National Institute of Neurological Diseases and Stroke grants P50 NS23393, PO1 NS42345, RO1 NS48349, RO1 NS38292, RO1 NS43324, and HL64766, and the Mort and Brigitte Harris Foundation.

Lian Li1, Quan Jiang1, Guangliang Ding1, Li Zhang1, Zheng Gang Zhang1, Qingjiang Li1, Swayamprava Panda1, Mei Lu2, James R Ewing1 and Michael Chopp1,3

  1. 1Department of Neurology, Henry Ford Hospital, Detroit, Michigan, USA
  2. 2Department of Biostatistics and Research Epidemiology, Henry Ford Hospital, Detroit, Michigan, USA
  3. 3Department of Physics, Oakland University, Rochester, Michigan, USA

Correspondence: Dr Q Jiang, B126, Education & Research Building, Department of Neurology, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA. E-mail: QJIANG1@hfhs.org

Received 7 August 2009; Revised 28 September 2009; Accepted 19 October 2009; Published online 4 November 2009.

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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.

Keywords:

administration route, lesion volume, MRI, neural progenitor cell, rat, transient ischemia

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