Abstract
Stroke is a leading cause of long-term disability worldwide, intensifying the need for effective recovery therapies. Stem cells are a promising stroke therapeutic, but creating ideal conditions for treatment is essential. Here we developed a conductive polymer system for stem cell delivery and electrical modulation in animals. Using this system, electrical modulation of human stem cell transplants improve functional stroke recovery in rodents. Increased endogenous stem cell production corresponds with improved function. Transcriptome analysis identified stanniocalcin 2 (STC2) as one of the genes most significantly upregulated by electrical stimulation. Lentiviral upregulation and downregulation of STC2 in the transplanted stem cells demonstrate that this glycoprotein is an essential mediator in the functional improvements seen with electrical modulation. Moreover, intraventricular administration of recombinant STC2 post-stroke confers functional benefits. In summation, our conductive polymer system enables electrical modulation of stem cells as a potential method to improve recovery and identify important therapeutic targets.
Highlights
Stroke is a leading cause of long-term disability worldwide, intensifying the need for effective recovery therapies
We optimized the conductive polymer system in vitro based on our previous work (Supplementary Fig. 2), where we found that VEGFA was a key trophic factor that gets upregulated with electrical stimulation in vitro[22]
Given stanniocalcin 2 (STC2) plays a role in cell proliferation and survival, we found it an interesting candidate to further explore its role in stroke recovery and the increase in endogenous stem cell production seen with combined stem cell delivery and electrical stimulation[35–39]
Summary
Stroke is a leading cause of long-term disability worldwide, intensifying the need for effective recovery therapies. We developed a conductive polymer system for stem cell delivery and electrical modulation in animals Using this system, electrical modulation of human stem cell transplants improve functional stroke recovery in rodents. Biomaterials are able to deliver important chemical factors or optimize stem cell delivery in therapeutic applications, but often lack the ability for continuous modulation after implantation[18–20] This single modality and static approach for neural rehabilitation juxtaposes the natural process of development, where an intricate combination of chemical, tactile, and electrical signals guide stem cells during brain formation. We demonstrate how the unique ability to continuously interact with the neural environment electrically via the conductive polymer provides further opportunity to shape the post-stroke brain to promote functional recovery
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