Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Canada.
Mol Pharm. 2012 May 7;9(5):1521-8. doi: 10.1021/mp300041k. Epub 2012 Apr 19.
This study reports the use of a nonviral expression system based on polyamidoamine dendrimers for time-restricted neurotrophin overproduction in mesenchymal stem cells and skin precursor-derived Schwann cells. The dendrimers were used to deliver plasmids for brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3) expression in both rodent and human stem cells, and the timelines of expression were studied. We have found that, despite the fact that transfection efficiencies and protein expression levels were comparable, dendrimer-driven expression in human mesenchymal stem cells was characterized by a more rapid decline compared to rodent cells. Transient expression systems can be beneficial for some neurotrophins, which were earlier reported to cause unwanted side effects in virus-based long-term expression models. Nonviral neurotrophin expression is a biologically safe and accessible alternative to increase the therapeutic potential of autologous adult stem cells and stem cell-derived functional differentiated cells.
本研究报告了一种基于聚酰胺-胺树枝状大分子的非病毒表达系统,用于在间充质干细胞和皮肤前体细胞衍生的雪旺细胞中限时过表达神经营养因子。该树枝状大分子被用于递送脑源性神经营养因子(BDNF)或神经营养因子-3(NT-3)的质粒,以在啮齿动物和人类干细胞中表达,并研究了表达的时间进程。我们发现,尽管转染效率和蛋白表达水平相当,但与啮齿动物细胞相比,树枝状大分子驱动的人骨髓间充质干细胞表达具有更快的下降趋势。瞬时表达系统对于某些神经营养因子可能是有益的,因为它们在基于病毒的长期表达模型中被报道会引起不必要的副作用。非病毒神经营养因子表达是一种生物安全且可及的替代方法,可以提高自体成体干细胞和干细胞衍生的功能分化细胞的治疗潜力。