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

Jonathan D. Proto, Aiping Lu, Akaitz Dorronsoro, Alex Scibetta, Paul D. Robbins, Laura J. Niedernhofer, Johnny Huard

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere0179270
JournalPloS one
Volume12
Issue number6
DOIs
StatePublished - Jun 2017
Externally publishedYes

Fingerprint

Stem cells
stress tolerance
Muscle
stem cells
Stem Cells
Muscles
muscles
mice
Cell Aging
Cell- and Tissue-Based Therapy
Aging of materials
Oxidative stress
therapeutics
Adult Stem Cells
Muscle Development
muscle development
Transcription Factors
Chemical activation
Tissue
Oxidative Stress

Cite this

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.

In: PloS one, Vol. 12, No. 6, e0179270, 06.2017.

Research output: Contribution to journalArticle

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. In: PloS one. 2017 ; Vol. 12, No. 6.
@article{9fa42f6d27fd47fa8f3d71d75f02b57f,
title = "Inhibition of NF-κB improves the stress resistance and myogenic differentiation of MDSPCs isolated from naturally aged mice",
abstract = "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.",
author = "Proto, {Jonathan D.} and Aiping Lu and Akaitz Dorronsoro and Alex Scibetta and Robbins, {Paul D.} and Niedernhofer, {Laura J.} and Johnny Huard",
year = "2017",
month = "6",
doi = "10.1371/journal.pone.0179270",
language = "English (US)",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - Inhibition of NF-κB improves the stress resistance and myogenic differentiation of MDSPCs isolated from naturally aged mice

AU - Proto, Jonathan D.

AU - Lu, Aiping

AU - Dorronsoro, Akaitz

AU - Scibetta, Alex

AU - Robbins, Paul D.

AU - Niedernhofer, Laura J.

AU - Huard, Johnny

PY - 2017/6

Y1 - 2017/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85021233747&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021233747&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0179270

DO - 10.1371/journal.pone.0179270

M3 - Article

C2 - 28640861

AN - SCOPUS:85021233747

VL - 12

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 6

M1 - e0179270

ER -