Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel; Medical School, The Hebrew University, Jerusalem, Israel.
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.
Neurobiol Aging. 2020 Nov;95:231-239. doi: 10.1016/j.neurobiolaging.2020.07.030. Epub 2020 Aug 6.
gCJD is a fatal late-onset neurodegenerative disease linked to mutations in the PRNP gene. We have previously shown that transplantation of neural precursor cells (NPCs), or administration of a nanoformulation of pomegranate seed oil (Nano-PSO, GranaGard), into newborn asymptomatic TgMHu2ME199K mice modeling for E200K gCJD significantly delayed the advance of clinical disease. In the present study, we tested the individual and combined effects of both treatments in older and sick TgMHu2ME199K mice. We show that while transplantation of NPCs at both initial (140 days) and advance clinical states (230 days) arrested disease progression for about 30 days, after which scores rapidly climbed to those of untreated Tgs, administration of Nano-PSO to transplanted TgMHu2ME199K mice resulted in detention of disease advance for 60-80 days, followed by a slower disease progression thereafter. Pathological examinations demonstrated the combined treatment extended the survival of the transplanted NPCs, and also increased the generation of endogenous stem cells. Our results suggest that administration of Nano-PSO may increase the beneficial effects of NPCs transplantation.
gCJD 是一种致命的晚发性神经退行性疾病，与 PRNP 基因突变有关。我们之前的研究表明，将神经前体细胞（NPCs）移植到新生无症状 TgMHu2ME199K 小鼠中，或给予石榴籽油纳米制剂（Nano-PSO，GranaGard），可显著延缓 E200K gCJD 模型的临床疾病进展。在本研究中，我们测试了这两种治疗方法单独和联合使用在老年和患病 TgMHu2ME199K 小鼠中的效果。我们发现，虽然 NPCs 的移植在初始（140 天）和进展的临床状态（230 天）时都能阻止疾病进展约 30 天，但之后评分迅速攀升至未治疗 Tgs 的水平，而将 Nano-PSO 给予移植的 TgMHu2ME199K 小鼠则可导致疾病进展延迟 60-80 天，此后疾病进展较慢。病理学检查表明，联合治疗延长了移植 NPCs 的存活时间，并增加了内源性干细胞的产生。我们的结果表明，Nano-PSO 的给予可能会增加 NPCs 移植的有益效果。
