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Inhibition of NF-κB improves the stress resistance and myogenic differentiation of MDSPCs isolated from naturally aged mice

A decline in the regenerative capacity of adult stem cells with aging is well documented. As a result of this decline, the efficacy of autologous stem cell therapies is likely to decline with increasing donor age. In these cases, strategies to restore the function of aged stem cells would have clini...

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Autores principales: Proto, Jonathan D., Lu, Aiping, Dorronsoro, Akaitz, Scibetta, Alex, Robbins, Paul D., Niedernhofer, Laura J., Huard, Johnny
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480862/
https://www.ncbi.nlm.nih.gov/pubmed/28640861
http://dx.doi.org/10.1371/journal.pone.0179270
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author Proto, Jonathan D.
Lu, Aiping
Dorronsoro, Akaitz
Scibetta, Alex
Robbins, Paul D.
Niedernhofer, Laura J.
Huard, Johnny
author_facet Proto, Jonathan D.
Lu, Aiping
Dorronsoro, Akaitz
Scibetta, Alex
Robbins, Paul D.
Niedernhofer, Laura J.
Huard, Johnny
author_sort Proto, Jonathan D.
collection PubMed
description A decline in the regenerative capacity of adult stem cells with aging is well documented. As a result of this decline, the efficacy of autologous stem cell therapies is likely to decline with increasing donor age. In these cases, strategies to restore the function of aged stem cells would have clinical utility. Globally, the transcription factor NF-κB is up-regulated in aged tissues. Given the negative role that NF-κB plays in myogenesis, we investigated whether the age-related decline in the function of muscle-derived stem/progenitor cells (MDSPCs) could be improved by inhibition of NF-κB. Herein, we demonstrate that pharmacologic or genetic inhibition of NF-κB activation increases myogenic differentiation and improves resistance to oxidative stress. Our results suggest that MDSPC “aging” may be reversible, and that pharmacologic targeting of pathways such as NF-κB may enhance the efficacy of cell-based therapies.
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spelling pubmed-54808622017-07-05 Inhibition of NF-κB improves the stress resistance and myogenic differentiation of MDSPCs isolated from naturally aged mice Proto, Jonathan D. Lu, Aiping Dorronsoro, Akaitz Scibetta, Alex Robbins, Paul D. Niedernhofer, Laura J. Huard, Johnny PLoS One Research Article A decline in the regenerative capacity of adult stem cells with aging is well documented. As a result of this decline, the efficacy of autologous stem cell therapies is likely to decline with increasing donor age. In these cases, strategies to restore the function of aged stem cells would have clinical utility. Globally, the transcription factor NF-κB is up-regulated in aged tissues. Given the negative role that NF-κB plays in myogenesis, we investigated whether the age-related decline in the function of muscle-derived stem/progenitor cells (MDSPCs) could be improved by inhibition of NF-κB. Herein, we demonstrate that pharmacologic or genetic inhibition of NF-κB activation increases myogenic differentiation and improves resistance to oxidative stress. Our results suggest that MDSPC “aging” may be reversible, and that pharmacologic targeting of pathways such as NF-κB may enhance the efficacy of cell-based therapies. Public Library of Science 2017-06-22 /pmc/articles/PMC5480862/ /pubmed/28640861 http://dx.doi.org/10.1371/journal.pone.0179270 Text en © 2017 Proto et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Proto, Jonathan D.
Lu, Aiping
Dorronsoro, Akaitz
Scibetta, Alex
Robbins, Paul D.
Niedernhofer, Laura J.
Huard, Johnny
Inhibition of NF-κB improves the stress resistance and myogenic differentiation of MDSPCs isolated from naturally aged mice
title Inhibition of NF-κB improves the stress resistance and myogenic differentiation of MDSPCs isolated from naturally aged mice
title_full Inhibition of NF-κB improves the stress resistance and myogenic differentiation of MDSPCs isolated from naturally aged mice
title_fullStr Inhibition of NF-κB improves the stress resistance and myogenic differentiation of MDSPCs isolated from naturally aged mice
title_full_unstemmed Inhibition of NF-κB improves the stress resistance and myogenic differentiation of MDSPCs isolated from naturally aged mice
title_short Inhibition of NF-κB improves the stress resistance and myogenic differentiation of MDSPCs isolated from naturally aged mice
title_sort inhibition of nf-κb improves the stress resistance and myogenic differentiation of mdspcs isolated from naturally aged mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480862/
https://www.ncbi.nlm.nih.gov/pubmed/28640861
http://dx.doi.org/10.1371/journal.pone.0179270
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