Berndt Marcus, Li Yongchao, Seyedhassantehrani Negar, Yao Li
Department of Biological Sciences, Wichita State University, Fairmount 1845, Wichita, KS, 67260, USA.
ACS Biomater Sci Eng. 2017 Jul 10;3(7):1313-1321. doi: 10.1021/acsbiomaterials.6b00229. Epub 2016 Jul 5.
Astrocytes play a critical role in supporting the normal physiological function of neurons. Recent studies have revealed that astrocyte transplantation can promote axonal regeneration and functional recovery after spinal cord injury. Biomaterial can be designed as a growth-permissive substrate and serve as a carrier for astrocyte transplantation into injured spinal cord. In this study, we developed a method to generate collagen microspheres encapsulating astrocytes by injecting a mixture of collagen and astrocytes into a cell culture medium with a syringe controlled by a syringe pump. The collagen microspheres were crosslinked with poly(ethylene glycol) ether tetrasuccinimidyl glutarate (4S-StarPEG) to reduce the degradation rate. The viability of cells in the crosslinked microspheres was higher than 90%. Astrocytes were transfected with plasmids encoding nerve growth factor (NGF)-ires-enhanced green fluorescent protein (EGFP) genes by electroporation and encapsulated in crosslinked microspheres. The level of NGF released into the cell culture medium was higher than that remaining in the microspheres or astrocytes. When microspheres encapsulating astrocytes transfected with plasmids encoding NGF-ires-EGFP genes were added into the cultured rat dorsal root ganglion, the axonal growth was significantly enhanced. This study shows that the microspheres can be potentially used as a carrier of astrocytes to promote nerve regeneration in injured neural tissue.
星形胶质细胞在支持神经元的正常生理功能中发挥着关键作用。最近的研究表明,星形胶质细胞移植可促进脊髓损伤后轴突再生和功能恢复。生物材料可被设计成一种允许生长的基质,并作为将星形胶质细胞移植到损伤脊髓中的载体。在本研究中,我们开发了一种通过用注射泵控制的注射器将胶原蛋白和星形胶质细胞的混合物注入细胞培养基中来生成包裹星形胶质细胞的胶原微球的方法。胶原微球与聚(乙二醇)醚四琥珀酰亚胺戊二酸酯(4S-StarPEG)交联以降低降解速率。交联微球中细胞的活力高于90%。通过电穿孔用编码神经生长因子(NGF)-内部核糖体进入位点-增强型绿色荧光蛋白(EGFP)基因的质粒转染星形胶质细胞,并将其包裹在交联微球中。释放到细胞培养基中的NGF水平高于保留在微球或星形胶质细胞中的水平。当将包裹有编码NGF-ires-EGFP基因的质粒转染的星形胶质细胞的微球添加到培养的大鼠背根神经节中时,轴突生长显著增强。本研究表明,微球有可能用作星形胶质细胞的载体,以促进损伤神经组织中的神经再生。