High-efficiency transfection and survival rates of embryonic and adult mouse neural stem cells achieved by electroporation

Authors:
Bettina Bertrama, Stefan Wiesea, Alexander von Holst
In:
Source: J Neurosci Methods
Publication Date: (2012)
Issue: 209(2): 420-427
Research Area:
Neurobiology
Stem Cells
Basic Research
Platform:
Nucleofector® I/II/2b
4D-Nucleofector® X-Unit
Experiment
For Lower cell number, 5E+5 neurosphere-derived NSCs were resuspended in 20µl P3 nucleofection solution containing 0.5 µg plasmid DNA. Cells were transferred into the nucleofector cuvette. After the pulse application, 180 µl prewarmed neurosphere medium was added to the electroporated NSCs in the cuvette. NSCs were gently resuspended in the cuvette and transferred into a sterile 1.5 ml tube. After centrifugation with 80×g for 5 min at room temperature, the supernatant was discarded and the cell pellet was resuspended in 500 µl neurosphere medium containing EGF and FGF2 (20 ng/ml). For higher cell numbers, 2.5–5E+6 neurosphere-derived NSCs were resuspended in 100 µl P3 nucleofection solution with 5 µg plasmid DNA and then nucleofected in the 100µl nucleofection cuvette. The transfected NSCs were resuspended in 500 µl prewarmed neurosphere medium, transferred to a 15 ml Falcon tube and centrifuged also at 80×g for 5 min at room temperature. The supernatant was discarded and the pellet was resuspended in neurosphere medium containing the same growth factors as above and cultivated as neurospheres over night at 37 °C.
Abstract
Cells of the central nervous system are notoriously difficult to transfect. This is not only true for neurons and glial cells but also for dividing neural stem and progenitor cells (NSCs). About ten years ago a major advance was provided by introduction of the nucleofection technology that allowed for transfection of approximately half of the exposed NSCs. However, limitations were encountered with the need for large numbers of NSCs for a single transfection and compromised survival rates with typically only one-third of the cells surviving the pulse conditions. Here, we report the establishment of a pulse protocol that targets NSCs with high efficiency and twofold higher NSC survival rates using the 4D Nucleofector device. We demonstrate that the established protocol not only provides a clear and significant improvement over existing protocols with transfection rates above 80% and two-thirds of the NSCs surviving for at least 48 h, but also their unaltered differentiation along neuronal and glial lineages. This improved protocol for the transfection of sensitive mouse central nervous system derived cells will provide an important step forward for studies of gene function by overexpression or knock-down of genes in cultured NSCs.