From the Departments of Pharmacology (M.A.E., H.A.K., H.X.C., C.V.G.-M., K.W.E.T., C.T.C., V.H.B., S.L., Q.N.D., A.V., G.R.D., C.G.S., B.R.S.B.), Obstetrics and Gynaecology (R.L., E.M.W.), Surgery (A.V., G.R.D., C.G.S.), and Medicine (T.G.P., V.K.S.), Australian Regenerative Medicine Institute (W.K., L.T., J.A.B.), and Monash Institute of Pharmaceutical Sciences (C.P.J.H., C.W.P., J.M.H.), Monash University, Victoria, Australia; Department of Physiology, Anatomy and Microbiology, La Trobe University, Victoria, Australia (M.A.E., H.A.K., Q.N.D., A.V., G.R.D., C.G.S.); The Ritchie Centre, Hudson Institute of Medical Research, Victoria, Australia (R.L., E.M.W.); Stroke Unit (T.G.P., V.K.S., H.M.) and Monash Women's Services (E.M.W.), Monash Health, Victoria, Australia; Menzies Research Institute, Tasmania, Australia (V.K.S.); Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore (T.V.A., D.Y.F., L.P.); School of Pharmacy, Sungkyunkwan University, Seoul, South Korea (T.V.A.); School of Health and Biomedical Sciences, RMIT University, Victoria, Australia (S.S.); Department of Anatomy, Brain Health Research Centre and Brain Research New Zealand (S.N., E.K.G., A.N.C.) and Department of Pathology (S.N.;S.Y.;A.N.C.), University of Otago, Dunedin, New Zealand; and Faculty of Pharmacy, University of Sydney, NSW, Australia (A.N.C.).
Stroke. 2018 Mar;49(3):700-709. doi: 10.1161/STROKEAHA.117.019136. Epub 2018 Jan 30.
BACKGROUND AND PURPOSE: Human amnion epithelial cells (hAECs) are nonimmunogenic, nontumorigenic, anti-inflammatory cells normally discarded with placental tissue. We reasoned that their profile of biological features, wide availability, and the lack of ethical barriers to their use could make these cells useful as a therapy in ischemic stroke. METHODS: We tested the efficacy of acute (1.5 hours) or delayed (1-3 days) poststroke intravenous injection of hAECs in 4 established animal models of cerebral ischemia. Animals included young (7-14 weeks) and aged mice (20-22 months) of both sexes, as well as adult marmosets of either sex. RESULTS: We found that hAECs administered 1.5 hours after stroke in mice migrated to the ischemic brain via a CXC chemokine receptor type 4-dependent mechanism and reduced brain inflammation, infarct development, and functional deficits. Furthermore, if hAECs administration was delayed until 1 or 3 days poststroke, long-term functional recovery was still augmented in young and aged mice of both sexes. We also showed proof-of-principle evidence in marmosets that acute intravenous injection of hAECs prevented infarct development from day 1 to day 10 after stroke. CONCLUSIONS: Systemic poststroke administration of hAECs elicits marked neuroprotection and facilitates mechanisms of repair and recovery.
背景与目的：人羊膜上皮细胞（hAECs）是非免疫原性、非致瘤性、抗炎细胞，通常在胎盘组织中被丢弃。我们推断，这些细胞具有生物学特征、广泛可用性和使用上不存在伦理障碍等特点，这使得它们有可能成为缺血性中风的一种治疗方法。
方法：我们在 4 种已建立的脑缺血动物模型中测试了急性（1.5 小时）或延迟（1-3 天）脑卒中后静脉注射 hAECs 的疗效。实验动物包括年轻（7-14 周）和年老（20-22 个月）的雄性和雌性小鼠，以及成年狨猴的雄性和雌性。
结果：我们发现，在小鼠中风后 1.5 小时给予 hAECs，可通过 CXC 趋化因子受体 4 依赖性机制迁移到缺血性大脑，并减少脑炎症、梗死发展和功能缺陷。此外，如果 hAECs 的给药延迟到脑卒中后 1 天或 3 天，仍能增强年轻和年老的雄性和雌性小鼠的长期功能恢复。我们还在狨猴中证明了初步的原理证据，即急性静脉注射 hAECs 可防止脑卒中后第 1 天至第 10 天的梗死发展。
结论：脑卒中后系统给予 hAECs 可引起明显的神经保护作用，并促进修复和恢复机制。
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