LAUSR

Objectives: We have previously found that intravenously injected human amnion epithelial cells (hAECs) provide neuroprotection following stroke by reducing inflammation and apoptosis. However, little is known about the factors these cells release to elicit neuroprotection. Interestingly, exosomes secreted by hAECs have been shown to have anti-inflammatory and regenerative properties as well as having an improved safety profile compared with their parent cell. Thus, the aim was to test whether delayed administration of amniotic exosomes reduce brain injury and enhance functional recovery following ischemic stroke. Methods: Male mice (8–12 weeks old) were subjected to photothrombotic stroke (n = 17) or sham surgery (n = 8). At 1 day post-stroke, mice were injected intravenously with vehicle (saline; n = 10) or 10 &mgr;g of amniotic exosomes (n = 7). Functional outcomes were assessed at 3 and 7 days post-stroke, after which the mice were euthanized and the brains removed. Infarct volume was assessed by thionin staining and immune cell infiltration was determined via immunohistochemistry. Results: 3 days post-stroke, mice treated with amniotic exosomes were able to grip a wire for 40% longer compared to mice treated with vehicle (p < 0.05), although significance was lost by 7 days. Infarct volume was strikingly reduced by 71 % (p < 0.05) following exosome administration compared to vehicle. Consistent with these data, amniotic exosomes reduced the number of infiltrating neutrophils and macrophages/microglia within the ischemic hemisphere. Finally, exosomes attenuated stroke-induced glial scar formation as well as neuronal apoptosis. Conclusion: These data indicate that delayed post-stroke administration of amniotic exosomes are neuroprotective and are thus a potentially safer and more viable stroke therapy than hAECs.