Li Xiaoguang, Yang Zhaoyang, Zhang Aifeng
Beijing Institute for Neuroscience, Capital Medical University, Beijing 100069, China.
Biomaterials. 2009 Oct;30(28):4978-85. doi: 10.1016/j.biomaterials.2009.05.047. Epub 2009 Jun 18.
In this study, the behavior of neural stem cells from the newborn rat spinal cord was compared at neurosphere level after the addition of neurotrophin-3 (NT-3) once or daily, blank chitosan carriers, or NT-3-chitosan carriers respectively. We found that NT-3 enhanced the viability and differentiation of neural stem cells, but as NT-3 has an extremely short half-life at 37 degrees C, in order to maintain the NT-3-mediated proliferation and differentiation effects on neural stem cells, NT-3 needed to be added to the medium every 24 h. However, NT-3-chitosan carriers dramatically increase the differentiation percentage of neural stem cells into neurons, which includes GABAergic and as cholinergic neurons. Although blank chitosan carriers also showed good biocompatibility to the neural stem cells, they induced the differentiation of these cells into neurons at a much lower percentage than the daily addition of NT-3 or the NT-3-chitosan carriers. Our results suggest that NT-3-chitosan carriers may not only maintain the viability of neural stem cells and increase their differentiation percentage into neurons, but also reduce the amount of NT-3 required for the survival and differentiation of these cells. These results may provide an experimental basis for the maximum replacement of dead neurons by neural stem cell transplant after spinal cord injury (SCI).
在本研究中,分别添加一次或每日添加神经营养因子-3(NT-3)、空白壳聚糖载体或NT-3-壳聚糖载体后,在神经球水平比较了新生大鼠脊髓神经干细胞的行为。我们发现,NT-3可增强神经干细胞的活力和分化能力,但由于NT-3在37℃时半衰期极短,为维持NT-3对神经干细胞的增殖和分化作用,需要每24小时向培养基中添加一次NT-3。然而,NT-3-壳聚糖载体显著提高了神经干细胞向神经元的分化百分比,其中包括γ-氨基丁酸能神经元和胆碱能神经元。虽然空白壳聚糖载体对神经干细胞也表现出良好的生物相容性,但它们诱导这些细胞向神经元分化的百分比远低于每日添加NT-3或NT-3-壳聚糖载体。我们的结果表明,NT-3-壳聚糖载体不仅可以维持神经干细胞的活力并提高其向神经元的分化百分比,还可以减少这些细胞存活和分化所需的NT-3量。这些结果可能为脊髓损伤(SCI)后通过神经干细胞移植最大限度替代死亡神经元提供实验依据。