The aim of the study was to establish electrical stimulation parameters in order to improve cell growth and viability of human adipose-derived stem cells (hADSC) when compared to non-stimulated cells in vitro. hADSC were exposed to continuous electrical stimulation with 1.7 V AC/20 Hz. After 24, 72 h and 7 days, cell number, cellular surface coverage and cell proliferation were assessed. In addition, cell cycle analysis was carried out after 3 and 7 days. After 24 h, no significant alterations were observed for stimulated cells. At day 3, stimulated cells showed a 4.5-fold increase in cell numbers, a 2.7-fold increase in cellular surface coverage and a significantly increased proliferation. Via cell cycle analysis, a significant increase in the G2/M phase was monitored for stimulated cells. Contrastingly, after 7 days, the non-stimulated group exhibited a 11-fold increase in cell numbers and a 4-fold increase in cellular surface coverage as well as a significant increase in cell proliferation. Moreover, the stimulated cells displayed a shift to the G1 and sub-G1 phase, indicating for metabolic arrest and apoptosis initiation. In accordance, continuous electrical stimulation of hADSC led to a significantly increased cell growth and proliferation after 3 days. However, longer stimulation periods such as 7 days caused an opposite result indicating initiation of apoptosis.

Context. Long-term deep brain stimulation (DBS) studies in rodents are of crucial importance for research progress in this field. However, most stimulation devices require jackets or large head-mounted systems which severely affect mobility and general welfare influencing animals’ behavior. Objective. To develop a preclinical neurostimulation implant system for long-term DBS research in small animal models. Approach. We propose a low-cost dual-channel DBS implant called software defined implantable platform (STELLA) with a printed circuit board size of Ø13 × 3.3 mm, weight of 0.6 g and current consumption of 7.6 µA/3.1 V combined with an epoxy resin-based encapsulation method. Main results. STELLA delivers charge-balanced and configurable current pulses with widely used commercial electrodes. While in vitro studies demonstrate at least 12 weeks of error-free stimulation using a CR1225 battery, our calculations predict a battery lifetime of up to 3 years using a CR2032. Exemplary application for DBS of the subthalamic nucleus in adult rats demonstrates that fully-implanted STELLA neurostimulators are very well-tolerated over 42 days without relevant stress after the early postoperative phase resulting in normal animal behavior. Encapsulation, external control and monitoring of function proved to be feasible. Stimulation with standard parameters elicited c-Fos expression by subthalamic neurons demonstrating biologically active function of STELLA. Significance. We developed a fully implantable, scalable and reliable DBS device that meets the urgent need for reverse translational research on DBS in freely moving rodent disease models including sensitive behavioral experiments. We thus add an important technology for animal research according to ‘The Principle of Humane Experimental Technique’—replacement, reduction and refinement (3R). All hardware, software and additional materials are available under an open source license.