Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex

S. Kelly, T. M. Bliss, A. K. Shah, G. H. Sun, M. Ma, W. C. Foo, J. Masel, M. A. Yenari, I. L. Weissman, N. Uchida, T. Palmer, G. K. Steinberg

Research output: Contribution to journalArticlepeer-review

524 Scopus citations

Abstract

We characterize the survival, migration, and differentiation of human neurospheres derived from CNS stem cells transplanted into the ischemic cortex of rats 7 days after distal middle cerebral artery occlusion. Transplanted neurospheres survived robustly in naive and ischemic brains 4 wk posttransplant. Survival was influenced by proximity of the graft to the stroke lesion and was negatively correlated with the number of IB4-positive inflammatory cells. Targeted migration of the human cells was seen in ischemic animals, with many human cells migrating long distances (≈1.2 mm) predominantly toward the lesion; in naive rats, cells migrated radially from the injection site in smaller number and over shorter distances (0.2 mm). The majority of migrating cells in ischemic rats had a neuronal phenotype. Migrating cells between the graft and the lesion expressed the neuroblast marker doublecortin, whereas human cells at the lesion border expressed the immature neuronal marker β-tubulin, although a small percentage of cells at the lesion border also expressed glial fibrillary acid protein (GFAP). Thus, transplanted human CNS (hCNS)-derived neurospheres survived robustly in naive and ischemic brains, and the microenvironment influenced their migration and fate.

Original languageEnglish (US)
Pages (from-to)11839-11844
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number32
DOIs
StatePublished - Aug 10 2004
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex'. Together they form a unique fingerprint.

Cite this