Effects of FTY720 on Neural Cell Behavior in Two and Three-Dimensional Culture and in Compression Spinal Cord Injury.

IF 2.3 4区医学 Q3 BIOPHYSICS Cellular and molecular bioengineering Pub Date : 2022-04-08 eCollection Date: 2022-08-01 DOI:10.1007/s12195-022-00724-0

Zahra Zeraatpisheh, Fatemeh Shamsi, Parisa Sarkoohi, Somayyeh Torabi, Hamed Alipour, Hadi Aligholi

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Abstract

Introduction: The present study aimed to evaluate the effects of FTY720 as a neuromodulatory drug on the behaviors of neural stem/progenitor cells (NS/PCs) in two-dimensional (2-D) and three-dimensional (3-D) cultures and in spinal cord injury (SCI).

Methods: The NS/PCs isolated from the ganglionic eminence of the 13.5-day old embryos were cultured as free-floating spheres. The single cells obtained from the second passage were cultured in 96-well plates without any scaffold (2-D) or containing PuraMatrix (PM, 3-D) or were used for transplantation in a mouse model of compression SCI. After exposure to 0, 10, 50, and 100 nanomolar of FTY720, the survival, proliferation, and migration of the NS/PCs were evaluated in vitro using MTT assay, neurosphere assay, and migration assay, respectively. Moreover, the functional recovery, survival and migration capacity of transplanted cells exposure to 100 nanomolar FTY720 were investigated in SCI.

Results: Cell survival and migration capacity increased after exposure to 50 and 100 nanomolar FTY720. In addition, higher doses of FTY720 led to the formation of more extensive and more neurospheres. Although this phenomenon was similar in both 2-D and 3-D cultures, PM induced better distribution of the cells in a 3-D environment. Furthermore, co-administration of FTY720 and NS/PCs 7 days after SCI enhanced functional recovery and both survival and migration of transplanted cells in the lesion site.

Conclusions: Due to the positive effects of FTY720 on the behavior of NS/PCs, using them in combination therapies can be an appealing approach for stem cell therapy in CNS injury.

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FTY720 对二维和三维培养及压迫性脊髓损伤中神经细胞行为的影响

引言本研究旨在评估神经调节药物 FTY720 在二维（2-D）和三维（3-D）培养以及脊髓损伤（SCI）中对神经干/祖细胞（NS/PCs）行为的影响：方法：从13.5天大胚胎的神经节突起中分离出的NS/PCs以自由浮动球的形式进行培养。从第二通道获得的单细胞在不含任何支架（2-D）或含PuraMatrix（PM，3-D）的96孔板中培养，或用于移植到小鼠压迫性SCI模型中。在暴露于 0、10、50 和 100 纳摩尔的 FTY720 后，分别使用 MTT 试验、神经球试验和迁移试验对 NS/PCs 的存活、增殖和迁移进行了体外评估。此外，还在 SCI 中研究了暴露于 100 纳摩尔 FTY720 的移植细胞的功能恢复、存活和迁移能力：结果：暴露于 50 和 100 纳摩尔 FTY720 后，细胞存活率和迁移能力均有所提高。此外，较高剂量的 FTY720 会导致形成更广泛和更多的神经球。虽然这种现象在二维和三维培养物中相似，但 PM 能诱导细胞在三维环境中更好地分布。此外，在脊髓损伤7天后联合使用FTY720和NS/PCs可促进功能恢复，并提高移植细胞在损伤部位的存活率和迁移率：结论：由于FTY720对NS/PCs行为的积极影响，在中枢神经系统损伤的干细胞治疗中，使用它们进行联合治疗是一种有吸引力的方法。

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来源期刊

Cellular and molecular bioengineering 生物-生物物理

CiteScore

5.60

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.