Abstract WP108: Effect Of Human Amnion Epithelial Cell Therapy On Stroke Outcome In Mice
Stem cells derived from human tissue, including embryonic, induced pluripotent, neural, and mesenchymal cells, have been reported to rescue injured brain tissue and improve functional recovery in experimental models of stroke. However, potentially major limitations to each of these cell types may limit their use as a treatment option for stroke patients. Conversely, stem cells derived from the placenta, namely human amnion epithelial cells (hAECs), which appear to offer several advantages over other stem cell lineages, have received almost no attention as a stroke therapy. We have tested the hypothesis that hAECs may be an effective form of cell-based therapy for stroke in male C57Bl6 mice subjected to 0.5 h middle cerebral artery occlusion-reperfusion. Mice were injected with 1x106 fluorescently-labelled hAECs or saline (vehicle) i.v. at either 1 h (acute treatment) or 72 h (delayed treatment) post-stroke and brains were removed after 3 or 14 d, respectively. Neurological and motor assessment tasks were performed every 3-4 days. hAECs injected acutely after stroke were present in the infarct, but not in the contralateral hemisphere at 72 h, and this was associated with improved neurological and motor function as well as reduced infarct damage (n = 7-12; P < 0.05). Immunofluorescence of the key marker of apoptosis, cleaved caspase-3, revealed that less apoptosis occurred in the infarct core of mice treated with hAECs versus vehicle (P < 0.05). Moreover, mice that instead received delayed post-stroke hAEC treatment had markedly improved survival and functional outcomes during 14 d compared with vehicle-treated mice (n = 10/group). Thus, early post-stroke i.v. delivery of hAECs can reduce brain injury and functional deficit. Delayed post-stroke hAEC treatment improves longer term survival and functional performance. These findings suggest that hAECs may be a viable and effective clinical therapy for promoting recovery following ischaemic stroke.
- © 2012 by American Heart Association, Inc.