Distler Thomas, Lauria Ines, Detsch Rainer, Sauter Clemens M, Bendt Farina, Kapr Julia, Rütten Stephan, Boccaccini Aldo R, Fritsche Ellen
Department of Materials Science and Engineering, Institute Biomaterials, University of Erlangen-Nuremberg, Cauerstr. 6, 91058 Erlangen, Germany.
IUF-Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225 Duesseldorf, Germany.
Biomedicines. 2021 Mar 5;9(3):261. doi: 10.3390/biomedicines9030261.
Biodegradable hydrogels that promote stem cell differentiation into neurons in three dimensions (3D) are highly desired in biomedical research to study drug neurotoxicity or to yield cell-containing biomaterials for neuronal tissue repair. Here, we demonstrate that oxidized alginate-gelatin-laminin (ADA-GEL-LAM) hydrogels facilitate neuronal differentiation and growth of embedded human induced pluripotent stem cell (hiPSC) derived neurospheres. ADA-GEL and ADA-GEL-LAM hydrogels exhibiting a stiffness close to ~5 kPa at initial cell culture conditions of 37 °C were prepared. Laminin supplemented ADA-GEL promoted an increase in neuronal differentiation in comparison to pristine ADA-GEL, with enhanced neuron migration from the neurospheres to the bulk 3D hydrogel matrix. The presence of laminin in ADA-GEL led to a more than two-fold increase in the number of neurospheres with migrated neurons. Our findings suggest that laminin addition to oxidized alginate-gelatin hydrogel matrices plays a crucial role to tailor oxidized alginate-gelatin hydrogels suitable for 3D neuronal cell culture applications.
在生物医学研究中，为了研究药物神经毒性或生产用于神经元组织修复的含细胞生物材料，非常需要能够促进干细胞在三维（3D）空间中分化为神经元的可生物降解水凝胶。在此，我们证明氧化海藻酸盐-明胶-层粘连蛋白（ADA-GEL-LAM）水凝胶可促进嵌入的人诱导多能干细胞（hiPSC）衍生神经球的神经元分化和生长。制备了在37°C的初始细胞培养条件下刚度接近约5 kPa的ADA-GEL和ADA-GEL-LAM水凝胶。与原始ADA-GEL相比，添加层粘连蛋白的ADA-GEL促进了神经元分化的增加，神经元从神经球向整体3D水凝胶基质的迁移增强。ADA-GEL中层粘连蛋白的存在导致具有迁移神经元的神经球数量增加了两倍多。我们的研究结果表明，除了氧化海藻酸盐-明胶水凝胶基质外，层粘连蛋白在定制适用于3D神经元细胞培养应用的氧化海藻酸盐-明胶水凝胶方面起着关键作用。
