Preconditioning promotes survival and angiomyogenic potential of mesenchymal stem cells in the infarcted heart via NF-κB signaling

Muhammad R. Afzal, Husnain Kh Haider, Niagara Muhammad Idris, Shujia Jiang, Rafeeq P.H. Ahmed, Muhammad Ashraf

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

We proposed that pharmacological manipulation of mesenchymal stem cells (MSCs) with diazoxide enhanced their survival and regenerative potential via NFκB regulation. MSCs preconditioned (PCMSCs) with diazoxide and later subjected to oxidant stress with 100μmol/L H2O 2 either immediately or after 24h exhibited higher survival (p<0.01 vs nonpreconditioned MSCs; Non-PCMSCs) 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 PCMSCs 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 PCMSCs viability at both early and 24h time-points. However, inhibition of NF-κB reduced viability of PCMSCs only at 24h time-point. For in vivo studies, DMEM without cells (group-1) or containing 1×106 male Non-PCMSCs (group-2), PCMSCs (group-3), PCMSCs 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 PCMSCs survival and angiomyogenic potential in the infarcted heart.

Original languageEnglish (US)
Pages (from-to)693-702
Number of pages10
JournalAntioxidants and Redox Signaling
Volume12
Issue number6
DOIs
StatePublished - Mar 15 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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