Introduction: Brain stimulation techniques to enhance stroke recovery are a promising area of research; however, in vivo electrical stimulation combined with neural progenitor cell (NPC) transplantation has not been fully investigated. We propose the use of a conductive polymer scaffold to optimize stem cell therapy and determine mechanisms driving stroke recovery.
Methods: The conductive polymer system consisting of a polypyrrole scaffold was seeded with NPCs (Aruna Biomedical) and implanted along with a reference electrode (Fig. 1a). Immunocompromised rats underwent a distal middle cerebral artery occlusion stroke. After 1 week post-stroke, implantation surgeries were performed. Electrical stimulation (AC: ±400 mV/100Hz for 1 hr, starting 1 day after implantation, n=10) was applied daily for 3 consecutive days. Blinded, behavior testing was performed for 6 weeks. Immunostaining was performed to determine endogenous NPC population (anti-BrdU, Abcam).
Results: We designed a cannula system to deliver NPCs with in vivo electrical stimulation (Fig. 1a). Electrically stimulated NPCs (NPC+ES) had an earlier recovery than the other groups (Fig. 1b). The unstimulated NPCs (NPC) also outperformed the cannula with the electrical stimulation alone (Polymer+ES), the cannula alone (Polymer), and the sham (Sham) groups. Combined NPC+ES increased post-stroke endogenous stem cells production in the subventricular zones (SVZ) (Fig. 1b,c).
Conclusion: In conclusion, electrical stimulation of NPCs via a conductive polymer implant enhances stroke recovery and increases endogenous stem cell production. Our platform enables the manipulation of NPCs in vivo to optimize recovery and evaluate the important mechanisms for functional improvement.