The
transplantation of neural precursor cells (NPCs) is known to be a promising approach to ameliorating behavioral deficits after
stroke in a rodent model of
middle cerebral artery occlusion (MCAo). Previous studies have shown that transplanted NPCs migrate toward the
infarct region, survive and differentiate into mature neurons to some extent. However, the spatiotemporal dynamics of NPC migration following
transplantation into
stroke animals have yet to be elucidated. In this study, we investigated the fates of human embryonic stem cell (hESC)-derived NPCs (ENStem-A) for 8 weeks following
transplantation into the side contralateral to the
infarct region using 7.0T animal magnetic resonance imaging (MRI). T2- and T2*-weighted MRI analyses indicated that the migrating cells were clearly detectable at the
infarct boundary zone by 1 week, and the intensity of the MRI signals robustly increased within 4 weeks after
transplantation. Afterwards, the signals were slightly increased or unchanged. At 8 weeks, we performed
Prussian blue staining and immunohistochemical staining using human-specific markers, and found that high percentages of transplanted cells migrated to the
infarct boundary. Most of these cells were CXCR4-positive. We also observed that the migrating cells expressed markers for various stages of neural differentiation, including
Nestin, Tuj1, NeuN, TH, DARPP-32 and SV38, indicating that the transplanted cells may partially contribute to the reconstruction of the damaged neural tissues after
stroke. Interestingly, we found that the extent of
gliosis (
glial fibrillary acidic protein-positive cells) and apoptosis (TUNEL-positive cells) were significantly decreased in the cell-transplanted group, suggesting that hESC-NPCs have a positive role in reducing glia
scar formation and cell death after
stroke. No
tumors formed in our study. We also performed various behavioral tests, including rotarod, stepping and modified neurological severity score tests, and found that the transplanted animals exhibited significant improvements in sensorimotor functions during the 8 weeks after
transplantation. Taken together, these results strongly suggest that hESC-NPCs have the capacity to migrate to the
infarct region, form neural tissues efficiently and contribute to behavioral recovery in a rodent model of
ischemic stroke.