Akbari Somayeh, Hooshmandi Etrat, Bayat Mahnaz, Borhani Haghighi Afshin, Salehi Mohammad Saied, Pandamooz Sareh, Yousefi Nejad Amirhossein, Haghani Masoud
Department of Physiology, The Medical School, Shiraz University of Medical Sciences, Shiraz, Iran.
Clinical Neurology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran.
Brain Res. 2022 Feb 1;1776:147750. doi: 10.1016/j.brainres.2021.147750. Epub 2021 Dec 9.
The incidence rate of senile dementia is rising, and there is no definite cure for it yet. Cell therapy, as a new investigational approach, has shown promising results. Hair bulges with abundant easily accessible neural stem cells permit autologous implantation in irreversible neurodegenerative disorders.
Fifty rats were randomly divided into 5 groups of control, sham-operation, two-common carotid vessel-occlusion rats that received vehicle (2VO + V), 2VO rats that received 1 × 10 epidermal stem cells (2VO + ESC1), and 2VO rats that received 2.5 × 10 epidermal stem cells (2VO + ESC2) in 300 µl PBS intravenously on days 4, 9, and 14 after surgery. The epidermal neural crest stem cells (EPI-NCSCs) were isolated from hair follicles of rat whiskers. The open-field, passive avoidance, and Morris water maze were used as behavioral tests. The basal-synaptic transmission, long-term potentiation (LTP), and short-term synaptic plasticity were evaluated by field-potential recording of the CA1 hippocampal area.
30 days after the first transplantation in the 2VO + ESC1 group, functional recovery was prominent in anxiety and fear memory compared to the 2VO + ESC2 group, while LTP induction was recovered in both groups of grafted animals without improvement in basal synaptic transmission. These positive recoveries may be related to the release of different neurotrophic factors from grafted cells that can stimulate endogenous neurogenesis and synaptic plasticity.
Our results showed that EPI-NCSCs implantation could rescue LTP and cognitive disability in 2VO rats, while transplantation of 1 million cells showed better performance relative to 2.5 million cells.
老年痴呆症的发病率正在上升,目前尚无确切的治愈方法。细胞疗法作为一种新的研究方法,已显示出有希望的结果。含有丰富且易于获取的神经干细胞的毛囊隆突允许在不可逆的神经退行性疾病中进行自体移植。
将50只大鼠随机分为5组:对照组、假手术组、接受载体的双侧颈总动脉闭塞大鼠(2VO + V)、接受1×10表皮干细胞的2VO大鼠(2VO + ESC1)以及在术后第4、9和14天经静脉注射300μl PBS中含2.5×10表皮干细胞的2VO大鼠(2VO + ESC2)。从大鼠胡须毛囊中分离表皮神经嵴干细胞(EPI - NCSCs)。采用旷场试验、被动回避试验和莫里斯水迷宫试验作为行为测试。通过海马CA1区的场电位记录评估基础突触传递、长时程增强(LTP)和短时程突触可塑性。
在2VO + ESC1组首次移植后30天,与2VO + ESC2组相比,焦虑和恐惧记忆方面的功能恢复显著,而两组移植动物的LTP诱导均恢复,但基础突触传递无改善。这些积极的恢复可能与移植细胞释放不同的神经营养因子有关,这些因子可刺激内源性神经发生和突触可塑性。
我们的结果表明,EPI - NCSCs植入可挽救2VO大鼠的LTP和认知障碍,而移植100万个细胞相对于250万个细胞表现出更好的效果。