Distribution pattern following systemic mesenchymal stem cell injection depends on the age of the recipient and neuronal health.
Distribution pattern following systemic mesenchymal stem cell injection depends on the age of the recipient and neuronal health.
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DOI：
10.1186/s13287-017-0533-2
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发表时间：
2017-04-18
影响因子：
7.5
通讯作者：
Stolzing A
中科院分区：
文献类型：
--
作者：
Fabian C;Naaldijk Y;Leovsky C;Johnson AA;Rudolph L;Jaeger C;Arnold K;Stolzing A
间充质干细胞（MSC）在许多不同的年龄相关的退行性疾病，包括阿尔茨海默病的治疗效果。目前对衰老是否影响MSC的移植效率知之甚少。在这项研究中，我们调查了静脉移植的同基因间充质干细胞来源于年轻和老年小鼠到年轻，老年和转基因APP/PS1阿尔茨海默病小鼠的分布。将来自雄性供体的MSC移植到雌性小鼠中，并使用Y染色体特异性探针通过PCR监测其分布模式。另外，通过免疫荧光和共聚焦显微镜证实了移植的MSC在APP/PS1小鼠脑中的生物分布。移植到幼年小鼠体内四周后，在肺、腋窝淋巴结、血液、肾、骨髓、脾、肝、心脏和脑皮质中发现了幼年MSC。相比之下，移植到老年小鼠中的年轻MSC仅在大脑皮层中发现。在年轻和老年小鼠受体中，老年MSC移植仅在血液和脾脏中显示生物分布。虽然年轻的移植MSC仅在年轻小鼠的大脑皮层中显示出神经元分布，但它们在APP/PS1小鼠的大脑中表现出广泛的神经元分布模式，并且在皮层、小脑、海马、嗅球和脑干中被发现。在APP/PS1小鼠的脑中，移植的MSC和驻留的小胶质细胞的免疫荧光信号是稳健的。单核细胞趋化因子-1水平在年轻小鼠的大脑皮层中最低，在APP/PS1小鼠中显著增加。在海马体内，老年小鼠的单核细胞趋化因子-1水平显着高于年轻小鼠和APP/PS1小鼠。我们在体内证明了移植后MSC的生物分布受衰老和神经元健康的影响。所用的受体和供体MSC的老化减弱了移植效率。临床上，我们的数据表明，老年人的骨髓间充质干细胞不应该用于移植，骨髓间充质干细胞移植到老年患者将是不太有效的。本文的在线版本（doi：10.1186/s13287-017-0533-2）包含补充材料，可供授权用户使用。
Mesenchymal stem cells (MSCs) show therapeutic efficacy in many different age-related degenerative diseases, including Alzheimer’s disease. Very little is currently known about whether or not aging impacts the transplantation efficiency of MSCs. In this study, we investigated the distribution of intravenously transplanted syngeneic MSCs derived from young and aged mice into young, aged, and transgenic APP/PS1 Alzheimer’s disease mice. MSCs from male donors were transplanted into female mice and their distribution pattern was monitored by PCR using Y-chromosome specific probes. Biodistribution of transplanted MSCs in the brains of APP/PS1 mice was additionally confirmed by immunofluorescence and confocal microscopy. Four weeks after transplantation into young mice, young MSCs were found in the lung, axillary lymph nodes, blood, kidney, bone marrow, spleen, liver, heart, and brain cortex. In contrast, young MSCs that were transplanted into aged mice were only found in the brain cortex. In both young and aged mouse recipients, transplantation of aged MSCs showed biodistribution only in the blood and spleen. Although young transplanted MSCs only showed neuronal distribution in the brain cortex in young mice, they exhibited a wide neuronal distribution pattern in the brains of APP/PS1 mice and were found in the cortex, cerebellum, hippocampus, olfactory bulb, and brainstem. The immunofluorescent signal of both transplanted MSCs and resident microglia was robust in the brains of APP/PS1 mice. Monocyte chemoattractant-1 levels were lowest in the brain cortex of young mice and were significantly increased in APP/PS1 mice. Within the hippocampus, monocyte chemoattractant-1 levels were significantly higher in aged mice compared with younger and APP/PS1 mice. We demonstrate in vivo that MSC biodistribution post transplantation is detrimentally affected by aging and neuronal health. Aging of both the recipient and the donor MSCs used attenuates transplantation efficiency. Clinically, our data would suggest that aged MSCs should not be used for transplantation and that transplantation of MSCs into aged patients will be less efficacious. The online version of this article (doi:10.1186/s13287-017-0533-2) contains supplementary material, which is available to authorized users.