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Magnetic targeted delivery of the SPIONs-labeled mesenchymal stem cells derived from human Wharton's jelly in Alzheimer's rat models.
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2020-02-22 , DOI: 10.1016/j.jconrel.2020.02.035 Farshid Qiyami Hour 1 , Amir Johari Moghadam 2 , Ali Shakeri-Zadeh 3 , Mehrdad Bakhtiyari 1 , Ronak Shabani 1 , Mehdi Mehdizadeh 1
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2020-02-22 , DOI: 10.1016/j.jconrel.2020.02.035 Farshid Qiyami Hour 1 , Amir Johari Moghadam 2 , Ali Shakeri-Zadeh 3 , Mehrdad Bakhtiyari 1 , Ronak Shabani 1 , Mehdi Mehdizadeh 1
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Alzheimer's disease (AD) as a progressive neurodegenerative disorder is one of the leading causes of death globally. Among all treatment approaches, mesenchymal stem cells (MSCs)-based therapy is a promising modality for neurological disorders including the AD. This study aimed to magnetically deliver human Wharton's jelly-derived MSCs (WJ-MSCs) toward the hippocampal area within the AD rat's brain and determine the effects of them in cognitive improvement. Rats were randomly divided into five groups as follow: vehicle-treated control, AD model (injection of 8 μg/kg of amyloid β 1-42), IV-NTC (treated with IV-injected Non-Targeted Cells), IV-TC (treated with IV-injected Targeted Cells), and ICV-NTC (treated with Intracerebroventricular-injected Non-Targeted Cells). WJ-MSCs were labeled with dextran-coated superparamagnetic iron oxide nanoparticles (dex-SPIONs, 50 μg/ml), by bio-mimicry method. SPIONs-labeled MSCs were highly prussian blue positive with an intracellular iron concentration of 2.9 ± 0.08 pg/cell, which were successfully targeted into the hippocampus of AD rats by a halbach magnet array as magnetic targeted cell delivery (MTCD) technique. Presence of SPIONs-labeled cells in hippocampal area was proved by magnetic resonance imaging (MRI) in which signal intensity was reduced by increasing the number of these cells. Behavioral examinations showed that WJ-MSCs caused memory and cognitive improvement. Also, histological assessments showed functional improvement of hippocampal cells by expression of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE). Overall, this study indicates MTCD approach as an alternative in MSC-based regenerative medicine because it approximately has the same results as invasive directly ICV-injection method has.
中文翻译：
在阿尔茨海默病大鼠模型中以磁性靶向递送源自人沃顿氏胶体的SPIONs标记的间充质干细胞。
阿尔茨海默氏病（AD）是一种进行性神经退行性疾病，是全球范围内主要的死亡原因之一。在所有治疗方法中，基于间充质干细胞（MSCs）的治疗方法对于包括AD在内的神经系统疾病都是一种有前途的方法。这项研究旨在将人沃顿氏胶冻来源的MSC（WJ-MSC）磁性传递到AD大鼠大脑内的海马区，并确定它们在认知改善中的作用。将大鼠随机分为五组，分别为：媒介物处理的对照组，AD模型（注射8μg/ kg的淀粉样蛋白1-42），IV-NTC（经静脉注射的非靶向细胞治疗），IV-TC （经IV注射的靶向细胞治疗）和ICV-NTC（经脑室内注射的非靶向细胞治疗）。通过生物模拟方法，用葡聚糖包被的超顺磁性氧化铁纳米颗粒（dex-SPIONs，50μg/ ml）标记WJ-MSC。SPIONs标记的MSCs为高度普鲁士蓝阳性，细胞内铁浓度为2.9±0.08 pg /细胞，通过halbach磁阵列作为磁性靶向细胞递送（MTCD）技术成功地将其靶向AD大鼠海马。通过磁共振成像（MRI）证明了海马区SPIONs标记的细胞的存在，其中通过增加这些细胞的数量来降低信号强度。行为学检查表明，WJ-MSC引起记忆力和认知能力的改善。此外，组织学评估显示胆碱乙酰转移酶（ChAT）和乙酰胆碱酯酶（AChE）的表达可改善海马细胞的功能。总体，
更新日期：2020-02-23
中文翻译：
在阿尔茨海默病大鼠模型中以磁性靶向递送源自人沃顿氏胶体的SPIONs标记的间充质干细胞。
阿尔茨海默氏病（AD）是一种进行性神经退行性疾病，是全球范围内主要的死亡原因之一。在所有治疗方法中，基于间充质干细胞（MSCs）的治疗方法对于包括AD在内的神经系统疾病都是一种有前途的方法。这项研究旨在将人沃顿氏胶冻来源的MSC（WJ-MSC）磁性传递到AD大鼠大脑内的海马区，并确定它们在认知改善中的作用。将大鼠随机分为五组，分别为：媒介物处理的对照组，AD模型（注射8μg/ kg的淀粉样蛋白1-42），IV-NTC（经静脉注射的非靶向细胞治疗），IV-TC （经IV注射的靶向细胞治疗）和ICV-NTC（经脑室内注射的非靶向细胞治疗）。通过生物模拟方法，用葡聚糖包被的超顺磁性氧化铁纳米颗粒（dex-SPIONs，50μg/ ml）标记WJ-MSC。SPIONs标记的MSCs为高度普鲁士蓝阳性，细胞内铁浓度为2.9±0.08 pg /细胞，通过halbach磁阵列作为磁性靶向细胞递送（MTCD）技术成功地将其靶向AD大鼠海马。通过磁共振成像（MRI）证明了海马区SPIONs标记的细胞的存在，其中通过增加这些细胞的数量来降低信号强度。行为学检查表明，WJ-MSC引起记忆力和认知能力的改善。此外，组织学评估显示胆碱乙酰转移酶（ChAT）和乙酰胆碱酯酶（AChE）的表达可改善海马细胞的功能。总体，
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