Abstract WP101: Localization of Stereotactic Injections of Human iNP cells One Week Post-MCAL Stroke is Critical in Reducing Stroke Lesion Injury
There is interest in therapeutic approaches to improve stroke injuries beyond the current 4.5 hour window of opportunity available for tPA treatment. We are interested in determining if neural progenitor cells can provide protection one week out from a stroke injury, and if the location of the cells relative to the core or penumbra of the injury site is important.
Methods: We used a unilateral permanent middle cerebral artery ligation (MCAL) stroke injury model in C57B6 mice (male 3 months old) that generates a modest cortical lesion with limited subcortical injury. A single 3 ul Stereotactic injection was made either in the stroke core, or outside the injury site penumbra under the ipsilateral hippocampus. We injected 100,000 neural progenitor cells (iNPs) differentiated from induced pluripotent stem cells derived from human fibroblasts. Previous work showed that injection in a matrix enhanced iNP survival, therefore, the cells were injected either in a hydrogel matrix (n=4) or in matrigel (n=5) one week post-MCAL. Hydrogel (n=5) and Matrigel (n=4) only control groups were also used. Mice were sacrificed three weeks post-MCAL (two weeks post-transplant) and evaluated for lesion size as a percent of cortex.
Results: Mice that received stem cells placed into the core of the lesion, regardless of the specific matrix, had significantly smaller cortical lesions (p=0.0021) than those who did not receive stem cells (hydrogel alone control 36.0% mean cortical lesion (10.7% SD); Hydrogel + iNP cells 15.6% (3.1%); Matrigel alone control 30.4% (10.0%), matrigel + iNP cells 19.4% (8.6%). There was no difference between the controls: saline only, matrigel only, or hydrogel only. Using the same approach a second set of mice received 100,000 iNP cells outside of the lesion site, below the ipsilateral hippocampus (matrigel + iNPs (n=9), matrigel alone (n=9), or saline (n=8). In contrast there was no reduction in lesion size.
Conclusion: This suggests that iNPs in the region of greatest injury can provide protection even one week following stroke, but that these effects are spatially limited. Future studies will focus on aged male and female populations.
- © 2012 by American Heart Association, Inc.