Journal
MOLECULAR PHARMACEUTICS
Volume 9, Issue 5, Pages 1521-1528Publisher
AMER CHEMICAL SOC
DOI: 10.1021/mp300041k
Keywords
BDNF; NT-3; transfection; PAMAM dendrimers; mesenchymal stem cells; skin precursor-derived Schwann cells
Funding
- Alberta Innovates-Health Solutions (AI-HS)
- Canadian Institute for Health Research (Regenerative Medicine and Nanomedicine Team) [163322]
- Center for Excellence in Nerve Regeneration
- ERA-NET [NAN2007-31198-E]
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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.
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