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

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

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

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.

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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