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

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 elect...

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Autores principales: Oh, Byeongtaek, Santhanam, Sruthi, Azadian, Matine, Swaminathan, Vishal, Lee, Alex G., McConnell, Kelly W., Levinson, Alexa, Song, Shang, Patel, Jainith J., Gardner, Emily E., George, Paul M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8924243/
https://www.ncbi.nlm.nih.gov/pubmed/35292643
http://dx.doi.org/10.1038/s41467-022-29017-w
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author Oh, Byeongtaek
Santhanam, Sruthi
Azadian, Matine
Swaminathan, Vishal
Lee, Alex G.
McConnell, Kelly W.
Levinson, Alexa
Song, Shang
Patel, Jainith J.
Gardner, Emily E.
George, Paul M.
author_facet Oh, Byeongtaek
Santhanam, Sruthi
Azadian, Matine
Swaminathan, Vishal
Lee, Alex G.
McConnell, Kelly W.
Levinson, Alexa
Song, Shang
Patel, Jainith J.
Gardner, Emily E.
George, Paul M.
author_sort Oh, Byeongtaek
collection PubMed
description 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.
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spelling pubmed-89242432022-04-01 Electrical modulation of transplanted stem cells improves functional recovery in a rodent model of stroke Oh, Byeongtaek Santhanam, Sruthi Azadian, Matine Swaminathan, Vishal Lee, Alex G. McConnell, Kelly W. Levinson, Alexa Song, Shang Patel, Jainith J. Gardner, Emily E. George, Paul M. Nat Commun Article 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. Nature Publishing Group UK 2022-03-15 /pmc/articles/PMC8924243/ /pubmed/35292643 http://dx.doi.org/10.1038/s41467-022-29017-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Oh, Byeongtaek
Santhanam, Sruthi
Azadian, Matine
Swaminathan, Vishal
Lee, Alex G.
McConnell, Kelly W.
Levinson, Alexa
Song, Shang
Patel, Jainith J.
Gardner, Emily E.
George, Paul M.
Electrical modulation of transplanted stem cells improves functional recovery in a rodent model of stroke
title Electrical modulation of transplanted stem cells improves functional recovery in a rodent model of stroke
title_full Electrical modulation of transplanted stem cells improves functional recovery in a rodent model of stroke
title_fullStr Electrical modulation of transplanted stem cells improves functional recovery in a rodent model of stroke
title_full_unstemmed Electrical modulation of transplanted stem cells improves functional recovery in a rodent model of stroke
title_short Electrical modulation of transplanted stem cells improves functional recovery in a rodent model of stroke
title_sort electrical modulation of transplanted stem cells improves functional recovery in a rodent model of stroke
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8924243/
https://www.ncbi.nlm.nih.gov/pubmed/35292643
http://dx.doi.org/10.1038/s41467-022-29017-w
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