There is increasing evidence that administration of many types of stem cells, including human amnion epithelial cells (hAECs), can reduce hypoxic‐ischemic injury, including in the perinatal brain. However, the therapeutic window for single dose treatment is not known. We compared the effects of early and delayed intracerebroventricular administration of hAECs in fetal sheep at 0.7 gestation on brain injury induced by 25 minutes of complete umbilical cord occlusion (UCO) or sham occlusion. Fetuses received either 1 × 10⁶ hAECs or vehicle alone, as an infusion over 1 hour, either 2 or 24 hours after UCO. Fetuses were killed for brain histology at 7 days post‐UCO. hAEC infusion at both 2 and 24 hours had dramatic anti‐inflammatory and anti‐gliotic effects, including significantly attenuating the increase in microglia after UCO in the white and gray matter and the number of astrocytes in the white matter. Both protocols partially improved myelination, but had no effect on total or immature/mature numbers of oligodendrocytes. Neuronal survival in the hippocampus was increased by hAEC infusion at either 2 or 24 hours, whereas only hAECs at 24 hours were associated with improved neuronal survival in the striatum and thalamus. Neither protocol improved recovery of electroencephalographic (EEG) power. These data suggest that a single infusion of hAECs is anti‐inflammatory, anti‐gliotic, and neuroprotective in preterm fetal sheep when given up to 24 hours after hypoxia‐ischemia, but was associated with limited white matter protection after 7 days recovery and no improvement in the recovery of EEG power.

中文翻译：

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人羊膜上皮干细胞减轻早产羊脐带闭塞后星形胶质细胞增生的机会之窗

越来越多的证据表明，施用多种类型的干细胞，包括人羊膜上皮细胞 (hAEC)，可以减少缺氧缺血性损伤，包括围产期大脑。然而，单剂量治疗的治疗窗口尚不清楚。我们比较了 0.7 胎羊早期和延迟脑室内给予 hAECs 对 25 分钟完全脐带闭塞 (UCO) 或假闭塞引起的脑损伤的影响。胎儿接受 1 × 10 ⁶hAECs 或单独的载体，作为 UCO 后 2 或 24 小时输注超过 1 小时。在 UCO 后 7 天处死胎儿进行脑组织学检查。在 2 小时和 24 小时输注 hAEC 具有显着的抗炎和抗胶质细胞作用，包括显着减弱 UCO 后白质和灰质中小胶质细胞的增加以及白质中星形胶质细胞的数量。两种方案都部分改善了髓鞘形成，但对少突胶质细胞的总数或未成熟/成熟数量没有影响。在 2 或 24 小时输注 hAEC 可增加海马神经元存活率，而只有 24 小时 hAEC 与纹状体和丘脑中神经元存活率的提高有关。两种方案都没有改善脑电图 (EEG) 功率的恢复。