15-07-08(18:45:03)
Authors:
Schewtschik S 1
Schaarschmidt G 1,2
Institutions:
1 Department of Neurology, University of Leipzig
2 Carl-Ludwig-Institut of Physiology, University of Leipzig
Title of abstract : De- and hyperpolarizing influences lead to functional neuronal development of human neural progenitor cells
Abstract text:
The most common method to treat persons with neurodegenerative disorders, e.g. Morbus Parkinson, is medicamentous. As these therapies are of limited success, combating only the resulting symptoms, cell replacement therapies are a promising strategy to compensate the underlying cell loss. The profit of such therapies relies on the availability of in vitro differentiated neurons, which we obtain from human neural progenitor cells (hNPCs). Differentiation of these cells in standard medium (DM) resulted in a limited functionality of the neurons. Thus, the aim of the present study was to optimize the neuronal in vitro differentiation. A new established two phase culturing protocol contains an initial week in a high potassium containing medium (DM-K), followed by another week in a low potassium and high sodium concentration (DM-Na). This procedure may mimic a physiological shift from depolarizing to hyperpolarizing conditions during brain development. Our results demonstrate that this strategy promotes the development of mature neuronal properties, including robust expression of various marker proteins, enhanced neurite outgrowth, sodium inward currents, and action potential firing. Therefore, de- and hyperpolarizing influences enable developing hNPCs to adopt mature functional qualities and to become a promising tool for stem cell therapy.
