Electrical modulation of transplanted stem cells improves functional recovery in a rodent model of stroke

Byeongtaek Oh, Sruthi Santhanam, Matine Azadian, Vishal Swaminathan, Alex G. Lee, Kelly W. McConnell, Alexa Levinson, Shang Song, Jainith J. Patel, Emily E. Gardner and Paul M. George ()
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Byeongtaek Oh: Stanford University School of Medicine
Sruthi Santhanam: Stanford University School of Medicine
Matine Azadian: Stanford University School of Medicine
Vishal Swaminathan: Stanford University School of Medicine
Alex G. Lee: University of California
Kelly W. McConnell: Stanford University School of Medicine
Alexa Levinson: Stanford University School of Medicine
Shang Song: Stanford University School of Medicine
Jainith J. Patel: Stanford University School of Medicine
Emily E. Gardner: Stanford University School of Medicine
Paul M. George: Stanford University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-29017-w

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