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Preconditioning Promotes Survival and Angiomyogenic Potential of Mesenchymal Stem Cells in the Infarcted Heart via NF-κB Signaling

We proposed that pharmacological manipulation of mesenchymal stem cells (MSCs) with diazoxide enhanced their survival and regenerative potential via NFκB regulation. MSCs preconditioned ( PC MSCs) with diazoxide and later subjected to oxidant stress with 100 μmol/L H 2 O 2 either immediately or afte... Full description

Journal Title: Antioxidants & redox signaling 2010, Vol.12 (6), p.693-702
Main Author: Afzal, Muhammad R.
Other Authors: Haider, Husnain Kh , Idris, Niagara Muhammad , Jiang, Shujia , Ahmed, Rafeeq P.H. , Ashraf, Muhammad
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Alma/SFX Local Collection
Publisher: 140 Huguenot Street, 3rd FloorNew Rochelle, NY 10801USA: Mary Ann Liebert, Inc
ID: ISSN: 1523-0864
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recordid: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2834442
title: Preconditioning Promotes Survival and Angiomyogenic Potential of Mesenchymal Stem Cells in the Infarcted Heart via NF-κB Signaling
format: Article
creator:
  • Afzal, Muhammad R.
  • Haider, Husnain Kh
  • Idris, Niagara Muhammad
  • Jiang, Shujia
  • Ahmed, Rafeeq P.H.
  • Ashraf, Muhammad
subjects:
  • Original Research Communications
ispartof: Antioxidants & redox signaling, 2010, Vol.12 (6), p.693-702
description: We proposed that pharmacological manipulation of mesenchymal stem cells (MSCs) with diazoxide enhanced their survival and regenerative potential via NFκB regulation. MSCs preconditioned ( PC MSCs) with diazoxide and later subjected to oxidant stress with 100 μmol/L H 2 O 2 either immediately or after 24 h exhibited higher survival ( p  
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 1523-0864
fulltext: fulltext
issn:
  • 1523-0864
  • 1557-7716
url: Link


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descriptionWe proposed that pharmacological manipulation of mesenchymal stem cells (MSCs) with diazoxide enhanced their survival and regenerative potential via NFκB regulation. MSCs preconditioned ( PC MSCs) with diazoxide and later subjected to oxidant stress with 100 μmol/L H 2 O 2 either immediately or after 24 h exhibited higher survival ( p  < 0.01 vs nonpreconditioned MSCs; Non-PC MSCs) with concomitantly increased phosphorylation of PI3K, Akt, GSK3β (cytoplasmic), and NF-κB (p65) (nuclear). Akt kinase activity was determined as a function of GSK3β activity. Pretreatment of PC MSCs with Wortmannin (Wt), NEMO-binding domain (NBD), or NF-κB (p50) siRNA abolished NF-κB (p65) activity. Preconditioning increased NF-κB-dependent elevation of secretable growth factors associated with their paracrine effects. Inhibition of PI3K activity with Wt reduced PC MSCs viability at both early and 24 h time-points. However, inhibition of NF-κB reduced viability of PC MSCs only at 24 h time-point. For in vivo studies, DMEM without cells (group-1) or containing 1 × 10 6 male Non-PC MSCs (group-2), PC MSCs (group-3), PC MSCs pretreated with Wortmannin (group-4) or NF-κB decoy (group-5) were transplanted in a female rat model of acute myocardial infarction. Group-3 showed highest cell survival and growth factor expression, increased angiomyogenesis, and functional improvement. We conclude that activation of NF-κB by preconditioning promoted PC MSCs survival and angiomyogenic potential in the infarcted heart. Antioxid. Redox Signal. 12, 693–702.
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abstractWe proposed that pharmacological manipulation of mesenchymal stem cells (MSCs) with diazoxide enhanced their survival and regenerative potential via NFκB regulation. MSCs preconditioned ( PC MSCs) with diazoxide and later subjected to oxidant stress with 100 μmol/L H 2 O 2 either immediately or after 24 h exhibited higher survival ( p  < 0.01 vs nonpreconditioned MSCs; Non-PC MSCs) with concomitantly increased phosphorylation of PI3K, Akt, GSK3β (cytoplasmic), and NF-κB (p65) (nuclear). Akt kinase activity was determined as a function of GSK3β activity. Pretreatment of PC MSCs with Wortmannin (Wt), NEMO-binding domain (NBD), or NF-κB (p50) siRNA abolished NF-κB (p65) activity. Preconditioning increased NF-κB-dependent elevation of secretable growth factors associated with their paracrine effects. Inhibition of PI3K activity with Wt reduced PC MSCs viability at both early and 24 h time-points. However, inhibition of NF-κB reduced viability of PC MSCs only at 24 h time-point. For in vivo studies, DMEM without cells (group-1) or containing 1 × 10 6 male Non-PC MSCs (group-2), PC MSCs (group-3), PC MSCs pretreated with Wortmannin (group-4) or NF-κB decoy (group-5) were transplanted in a female rat model of acute myocardial infarction. Group-3 showed highest cell survival and growth factor expression, increased angiomyogenesis, and functional improvement. We conclude that activation of NF-κB by preconditioning promoted PC MSCs survival and angiomyogenic potential in the infarcted heart. Antioxid. Redox Signal. 12, 693–702.
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