Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL, USA.
J Pineal Res. 2011 Apr;50(3):272-80. doi: 10.1111/j.1600-079X.2010.00837.x. Epub 2011 Jan 27.
Recent studies have demonstrated that the human placenta is a novel source of adult stem cells. We have provided laboratory evidence that transplantation of these human placenta-derived cells in vitro and in vivo stroke models promotes functional recovery. However, the mechanisms underlying these observed therapeutic benefits of human placenta-derived cells unfortunately remain poorly understood. Here, we examined the expression of two discrete types of melatonin receptors and their roles in proliferation and differentiation of cultured human amniotic epithelial cells (AECs). Cultured AECs express melatonin receptor type 1A (MT1), but not melatonin receptor type 1B (MT2). The proliferation of cultured AECs was increased in the melatonin-treated group in a dose-dependent manner, and the viability of cultured AECs could be further enhanced by melatonin. Moreover, the viability of AECs significantly decreased with H(2) O(2) exposure, which was reversed by pretreatment with melatonin, resulting in increased cell survival rate and cell proliferation. Immunocytochemically, administration of melatonin significantly suppressed nestin proliferation, but enhanced TUJ1 differentiation of MT1-expressing AECs. Additional experiments incorporating antibody blocking and synergistic AEC-melatonin treatments further showed AEC therapeutic benefits via MT1 modulation. Finally, analysis of trophic factors revealed cultured AECs secreted VEGF in the presence of melatonin. These data indicate that melatonin by stimulating MT1 increased cell proliferation and survival rate while enhancing neuronal differentiation of cultured AECs, which together with VEGF upregulation, rendered neuroprotection against experimental in vitro models of ischemic and oxidative stress injury.
最近的研究表明，人类胎盘是一种新的成人干细胞来源。我们已经提供了实验室证据，证明这些人胎盘来源的细胞在体外和体内中风模型中的移植可以促进功能恢复。然而，不幸的是，人胎盘来源的细胞观察到的治疗益处的机制仍未得到很好的理解。在这里，我们研究了两种不同类型的褪黑素受体的表达及其在培养的人羊膜上皮细胞（AEC）增殖和分化中的作用。培养的 AEC 表达褪黑素受体 1A（MT1），但不表达褪黑素受体 1B（MT2）。培养的 AEC 增殖在褪黑素处理组中呈剂量依赖性增加，而褪黑素可进一步增强培养的 AEC 活力。此外，AEC 的活力随着 H（2）O（2）暴露而显著降低，用褪黑素预处理可逆转，导致细胞存活率和细胞增殖增加。免疫细胞化学显示，褪黑素给药显著抑制巢蛋白的增殖，但增强 MT1 表达的 AEC 的 TUJ1 分化。通过抗体阻断和协同 AEC-褪黑素处理的进一步实验表明，通过 MT1 调节，AEC 具有治疗益处。最后，对营养因子的分析表明，培养的 AEC 在褪黑素存在的情况下分泌 VEGF。这些数据表明，褪黑素通过刺激 MT1 增加细胞增殖和存活率，同时增强培养的 AEC 的神经元分化，与 VEGF 的上调一起，对实验性体外缺血和氧化应激损伤模型提供神经保护。
