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Nanotransfection-based vasculogenic cell reprogramming drives functional recovery in a mouse model of ischemic stroke
Ischemic stroke causes vascular and neuronal tissue deficiencies that could lead to substantial functional impairment and/or death. Although progenitor-based vasculogenic cell therapies have shown promise as a potential rescue strategy following ischemic stroke, current approaches face major hurdles...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978431/ https://www.ncbi.nlm.nih.gov/pubmed/33741587 http://dx.doi.org/10.1126/sciadv.abd4735 |
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author | Lemmerman, Luke R. Balch, Maria H. H. Moore, Jordan T. Alzate-Correa, Diego Rincon-Benavides, Maria A. Salazar-Puerta, Ana Gnyawali, Surya Harris, Hallie N. Lawrence, William Ortega-Pineda, Lilibeth Wilch, Lauren Risser, Ian B. Maxwell, Aidan J. Duarte-Sanmiguel, Silvia Dodd, Daniel Guio-Vega, Gina P. McTigue, Dana M. Arnold, W. David Nimjee, Shahid M. Sen, Chandan K. Khanna, Savita Rink, Cameron Higuita-Castro, Natalia Gallego-Perez, Daniel |
author_facet | Lemmerman, Luke R. Balch, Maria H. H. Moore, Jordan T. Alzate-Correa, Diego Rincon-Benavides, Maria A. Salazar-Puerta, Ana Gnyawali, Surya Harris, Hallie N. Lawrence, William Ortega-Pineda, Lilibeth Wilch, Lauren Risser, Ian B. Maxwell, Aidan J. Duarte-Sanmiguel, Silvia Dodd, Daniel Guio-Vega, Gina P. McTigue, Dana M. Arnold, W. David Nimjee, Shahid M. Sen, Chandan K. Khanna, Savita Rink, Cameron Higuita-Castro, Natalia Gallego-Perez, Daniel |
author_sort | Lemmerman, Luke R. |
collection | PubMed |
description | Ischemic stroke causes vascular and neuronal tissue deficiencies that could lead to substantial functional impairment and/or death. Although progenitor-based vasculogenic cell therapies have shown promise as a potential rescue strategy following ischemic stroke, current approaches face major hurdles. Here, we used fibroblasts nanotransfected with Etv2, Foxc2, and Fli1 (EFF) to drive reprogramming-based vasculogenesis, intracranially, as a potential therapy for ischemic stroke. Perfusion analyses suggest that intracranial delivery of EFF-nanotransfected fibroblasts led to a dose-dependent increase in perfusion 14 days after injection. MRI and behavioral tests revealed ~70% infarct resolution and up to ~90% motor recovery for mice treated with EFF-nanotransfected fibroblasts. Immunohistological analysis confirmed increases in vascularity and neuronal cellularity, as well as reduced glial scar formation in response to treatment with EFF-nanotransfected fibroblasts. Together, our results suggest that vasculogenic cell therapies based on nanotransfection-driven (i.e., nonviral) cellular reprogramming represent a promising strategy for the treatment of ischemic stroke. |
format | Online Article Text |
id | pubmed-7978431 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-79784312021-03-31 Nanotransfection-based vasculogenic cell reprogramming drives functional recovery in a mouse model of ischemic stroke Lemmerman, Luke R. Balch, Maria H. H. Moore, Jordan T. Alzate-Correa, Diego Rincon-Benavides, Maria A. Salazar-Puerta, Ana Gnyawali, Surya Harris, Hallie N. Lawrence, William Ortega-Pineda, Lilibeth Wilch, Lauren Risser, Ian B. Maxwell, Aidan J. Duarte-Sanmiguel, Silvia Dodd, Daniel Guio-Vega, Gina P. McTigue, Dana M. Arnold, W. David Nimjee, Shahid M. Sen, Chandan K. Khanna, Savita Rink, Cameron Higuita-Castro, Natalia Gallego-Perez, Daniel Sci Adv Research Articles Ischemic stroke causes vascular and neuronal tissue deficiencies that could lead to substantial functional impairment and/or death. Although progenitor-based vasculogenic cell therapies have shown promise as a potential rescue strategy following ischemic stroke, current approaches face major hurdles. Here, we used fibroblasts nanotransfected with Etv2, Foxc2, and Fli1 (EFF) to drive reprogramming-based vasculogenesis, intracranially, as a potential therapy for ischemic stroke. Perfusion analyses suggest that intracranial delivery of EFF-nanotransfected fibroblasts led to a dose-dependent increase in perfusion 14 days after injection. MRI and behavioral tests revealed ~70% infarct resolution and up to ~90% motor recovery for mice treated with EFF-nanotransfected fibroblasts. Immunohistological analysis confirmed increases in vascularity and neuronal cellularity, as well as reduced glial scar formation in response to treatment with EFF-nanotransfected fibroblasts. Together, our results suggest that vasculogenic cell therapies based on nanotransfection-driven (i.e., nonviral) cellular reprogramming represent a promising strategy for the treatment of ischemic stroke. American Association for the Advancement of Science 2021-03-19 /pmc/articles/PMC7978431/ /pubmed/33741587 http://dx.doi.org/10.1126/sciadv.abd4735 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Lemmerman, Luke R. Balch, Maria H. H. Moore, Jordan T. Alzate-Correa, Diego Rincon-Benavides, Maria A. Salazar-Puerta, Ana Gnyawali, Surya Harris, Hallie N. Lawrence, William Ortega-Pineda, Lilibeth Wilch, Lauren Risser, Ian B. Maxwell, Aidan J. Duarte-Sanmiguel, Silvia Dodd, Daniel Guio-Vega, Gina P. McTigue, Dana M. Arnold, W. David Nimjee, Shahid M. Sen, Chandan K. Khanna, Savita Rink, Cameron Higuita-Castro, Natalia Gallego-Perez, Daniel Nanotransfection-based vasculogenic cell reprogramming drives functional recovery in a mouse model of ischemic stroke |
title | Nanotransfection-based vasculogenic cell reprogramming drives functional recovery in a mouse model of ischemic stroke |
title_full | Nanotransfection-based vasculogenic cell reprogramming drives functional recovery in a mouse model of ischemic stroke |
title_fullStr | Nanotransfection-based vasculogenic cell reprogramming drives functional recovery in a mouse model of ischemic stroke |
title_full_unstemmed | Nanotransfection-based vasculogenic cell reprogramming drives functional recovery in a mouse model of ischemic stroke |
title_short | Nanotransfection-based vasculogenic cell reprogramming drives functional recovery in a mouse model of ischemic stroke |
title_sort | nanotransfection-based vasculogenic cell reprogramming drives functional recovery in a mouse model of ischemic stroke |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978431/ https://www.ncbi.nlm.nih.gov/pubmed/33741587 http://dx.doi.org/10.1126/sciadv.abd4735 |
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