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Electrical Stimulation of pediatric cardiac‐derived c‐kit(+) progenitor cells improves retention and cardiac function in right ventricular heart failure
Nearly 1 in every 120 children born has a congenital heart defect. Although surgical therapy has improved survival, many of these children go on to develop right ventricular heart failure (RVHF). The emergence of cardiovascular regenerative medicine as a potential therapeutic strategy for pediatric...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916193/ https://www.ncbi.nlm.nih.gov/pubmed/31574184 http://dx.doi.org/10.1002/stem.3088 |
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author | Maxwell, Joshua T. Trac, David Shen, Ming Brown, Milton E. Davis, Michael E. Chao, Myra S. Supapannachart, Krittin J. Zaladonis, Carly A. Baker, Emily Li, Martin L. Zhao, Jennifer Jacobs, Daniel I. |
author_facet | Maxwell, Joshua T. Trac, David Shen, Ming Brown, Milton E. Davis, Michael E. Chao, Myra S. Supapannachart, Krittin J. Zaladonis, Carly A. Baker, Emily Li, Martin L. Zhao, Jennifer Jacobs, Daniel I. |
author_sort | Maxwell, Joshua T. |
collection | PubMed |
description | Nearly 1 in every 120 children born has a congenital heart defect. Although surgical therapy has improved survival, many of these children go on to develop right ventricular heart failure (RVHF). The emergence of cardiovascular regenerative medicine as a potential therapeutic strategy for pediatric HF has provided new avenues for treatment with a focus on repairing or regenerating the diseased myocardium to restore cardiac function. Although primarily tried using adult cells and adult disease models, stem cell therapy is relatively untested in the pediatric population. Here, we investigate the ability of electrical stimulation (ES) to enhance the retention and therapeutic function of pediatric cardiac‐derived c‐kit(+) progenitor cells (CPCs) in an animal model of RVHF. Human CPCs isolated from pediatric patients were exposed to chronic ES and implanted into the RV myocardium of rats. Cardiac function and cellular retention analysis showed electrically stimulated CPCs (ES‐CPCs) were retained in the heart at a significantly higher level and longer time than control CPCs and also significantly improved right ventricular functional parameters. ES also induced upregulation of extracellular matrix and adhesion genes and increased in vitro survival and adhesion of cells. Specifically, upregulation of β1 and β5 integrins contributed to the increased retention of ES‐CPCs. Lastly, we show that ES induces CPCs to release higher levels of pro‐reparative factors in vitro. These findings suggest that ES can be used to increase the retention, survival, and therapeutic effect of human c‐kit(+) progenitor cells and can have implications on a variety of cell‐based therapies. stem cells 2019;37:1528–1541 |
format | Online Article Text |
id | pubmed-6916193 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69161932019-12-17 Electrical Stimulation of pediatric cardiac‐derived c‐kit(+) progenitor cells improves retention and cardiac function in right ventricular heart failure Maxwell, Joshua T. Trac, David Shen, Ming Brown, Milton E. Davis, Michael E. Chao, Myra S. Supapannachart, Krittin J. Zaladonis, Carly A. Baker, Emily Li, Martin L. Zhao, Jennifer Jacobs, Daniel I. Stem Cells Regenerative Medicine Nearly 1 in every 120 children born has a congenital heart defect. Although surgical therapy has improved survival, many of these children go on to develop right ventricular heart failure (RVHF). The emergence of cardiovascular regenerative medicine as a potential therapeutic strategy for pediatric HF has provided new avenues for treatment with a focus on repairing or regenerating the diseased myocardium to restore cardiac function. Although primarily tried using adult cells and adult disease models, stem cell therapy is relatively untested in the pediatric population. Here, we investigate the ability of electrical stimulation (ES) to enhance the retention and therapeutic function of pediatric cardiac‐derived c‐kit(+) progenitor cells (CPCs) in an animal model of RVHF. Human CPCs isolated from pediatric patients were exposed to chronic ES and implanted into the RV myocardium of rats. Cardiac function and cellular retention analysis showed electrically stimulated CPCs (ES‐CPCs) were retained in the heart at a significantly higher level and longer time than control CPCs and also significantly improved right ventricular functional parameters. ES also induced upregulation of extracellular matrix and adhesion genes and increased in vitro survival and adhesion of cells. Specifically, upregulation of β1 and β5 integrins contributed to the increased retention of ES‐CPCs. Lastly, we show that ES induces CPCs to release higher levels of pro‐reparative factors in vitro. These findings suggest that ES can be used to increase the retention, survival, and therapeutic effect of human c‐kit(+) progenitor cells and can have implications on a variety of cell‐based therapies. stem cells 2019;37:1528–1541 John Wiley & Sons, Inc. 2019-10-22 2019-12 /pmc/articles/PMC6916193/ /pubmed/31574184 http://dx.doi.org/10.1002/stem.3088 Text en © 2019 The Authors. stem cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press 2019 This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Regenerative Medicine Maxwell, Joshua T. Trac, David Shen, Ming Brown, Milton E. Davis, Michael E. Chao, Myra S. Supapannachart, Krittin J. Zaladonis, Carly A. Baker, Emily Li, Martin L. Zhao, Jennifer Jacobs, Daniel I. Electrical Stimulation of pediatric cardiac‐derived c‐kit(+) progenitor cells improves retention and cardiac function in right ventricular heart failure |
title | Electrical Stimulation of pediatric cardiac‐derived c‐kit(+) progenitor cells improves retention and cardiac function in right ventricular heart failure |
title_full | Electrical Stimulation of pediatric cardiac‐derived c‐kit(+) progenitor cells improves retention and cardiac function in right ventricular heart failure |
title_fullStr | Electrical Stimulation of pediatric cardiac‐derived c‐kit(+) progenitor cells improves retention and cardiac function in right ventricular heart failure |
title_full_unstemmed | Electrical Stimulation of pediatric cardiac‐derived c‐kit(+) progenitor cells improves retention and cardiac function in right ventricular heart failure |
title_short | Electrical Stimulation of pediatric cardiac‐derived c‐kit(+) progenitor cells improves retention and cardiac function in right ventricular heart failure |
title_sort | electrical stimulation of pediatric cardiac‐derived c‐kit(+) progenitor cells improves retention and cardiac function in right ventricular heart failure |
topic | Regenerative Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916193/ https://www.ncbi.nlm.nih.gov/pubmed/31574184 http://dx.doi.org/10.1002/stem.3088 |
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