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

J Cereb Blood Flow Metab. 2010 Mar;30(3):653-62. doi: 10.1038/jcbfm.2009.238. Epub 2009 Nov 4.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / mortality
  • Brain Ischemia / pathology*
  • Brain Ischemia / therapy*
  • Cell Movement / physiology*
  • Cisterna Magna
  • Image Processing, Computer-Assisted
  • Injections
  • Injections, Intra-Arterial
  • Injections, Intravenous
  • Magnetic Resonance Imaging
  • Male
  • Neurons / transplantation*
  • Rats
  • Rats, Wistar
  • Stem Cell Transplantation / methods*
  • Stem Cell Transplantation / mortality
  • Tissue Fixation