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移植的嗅前体细胞的命运取决于共培养中受体脑组织的细胞表型。

The Fate of Transplanted Olfactory Progenitors Is Conditioned by the Cell Phenotypes of the Receiver Brain Tissue in Cocultures.

机构信息

Inserm UMR1256/NGERE, Faculté de Medecine, 9 Avenue de la Forêt de Haye, Université de Lorraine, F-54000 Nancy, France.

Laboratoire de Neurosciences, Place Leclerc, Université de Franche-Comté, F-25000 Besancon, France.

出版信息

Int J Mol Sci. 2020 Sep 30;21(19):7249. doi: 10.3390/ijms21197249.

DOI:10.3390/ijms21197249
PMID:33008128
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7582579/
Abstract

Among the numerous candidates for cell therapy of the central nervous system (CNS), olfactory progenitors (OPs) represent an interesting alternative because they are free of ethical concerns, are easy to collect, and allow autologous transplantation. In the present study, we focused on the optimization of neuron production and maturation. It is known that plated OPs respond to various trophic factors, and we also showed that the use of Nerve Growth Factor (NGF) allowed switching from a 60/40 neuron/glia ratio to an 80/20 one. Nevertheless, in order to focus on the integration of OPs in mature neural circuits, we cocultured OPs in primary cultures obtained from the cortex and hippocampus of newborn mice. When dissociated OPs were plated, they differentiated into both glial and neuronal phenotypes, but we obtained a 1.5-fold higher viability in cortex/OP cocultures than in hippocampus/OP ones. The fate of OPs in cocultures was characterized with different markers such as BrdU, Map-2, and Synapsin, indicating a healthy integration. These results suggest that the integration of transplanted OPs might by affected by trophic factors and the environmental conditions/cell phenotypes of the host tissue. Thus, a model of coculture could provide useful information on key cell events for the use of progenitors in cell therapy.

摘要

在众多中枢神经系统 (CNS) 细胞治疗的候选者中,嗅前体细胞 (OPs) 是一种很有前途的选择,因为它们没有伦理问题,易于采集,并且可以进行自体移植。在本研究中,我们专注于神经元的生产和成熟的优化。已知贴壁的 OPs 对各种营养因子有反应,我们还表明,使用神经生长因子 (NGF) 可以将神经元/神经胶质比例从 60/40 转变为 80/20。然而,为了关注 OPs 与成熟神经回路的整合,我们将 OPs 与从小鼠大脑皮层和海马体获得的原代培养物共培养。当分离的 OPs 被种植时,它们分化为神经胶质和神经元表型,但我们在皮层/OP 共培养物中获得了比海马体/OP 共培养物高 1.5 倍的细胞活力。通过不同的标志物(如 BrdU、Map-2 和 Synapsin)对共培养物中的 OPs 命运进行了表征,表明其整合是健康的。这些结果表明,移植 OPs 的整合可能受到营养因子和宿主组织的环境条件/细胞表型的影响。因此,共培养模型可以为使用祖细胞进行细胞治疗提供有关关键细胞事件的有用信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/499c/7582579/a7c237ea7b63/ijms-21-07249-g007.jpg
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The Astrocyte-Neuron Interface: An Overview on Molecular and Cellular Dynamics Controlling Formation and Maintenance of the Tripartite Synapse.星形胶质细胞-神经元界面:控制三方突触形成与维持的分子和细胞动力学概述。
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Injured adult motor and sensory axons regenerate into appropriate organotypic domains of neural progenitor grafts.
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