Preconditioning mesenchymal stem cells with caspase inhibition and hyperoxia prior to hypoxia exposure increases cell proliferation

Uksha Saini, Richard J Gumina, Brian Wolfe, M. Lakshmi Kuppusamy, Periannan Kuppusamy, Konstantinos Dean Boudoulas

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Myocardial infarction is a leading cause of mortality and morbidity worldwide. Occlusion of a coronary artery produces ischemia and myocardial necrosis that leads to left ventricular (LV) remodeling, dysfunction, and heart failure. Stem cell therapy may decrease infarct size and improve LV function; the hypoxic environment, however, following a myocardial infarction may result in apoptosis, which in turn decreases survival of transplanted stem cells. Therefore, the effects of preconditioned mesenchymal stem cells (MSC) with hyperoxia (100% oxygen), Z-VAD-FMK pan-caspase inhibitor (CI), or both in a hypoxic environment in order to mimic conditions seen in cardiac tissue post-myocardial infarction were studied in vitro. MSCs preconditioned with hyperoxia or CI significantly decreased apoptosis as suggested by TUNEL assay and Annexin V analysis using fluorescence assisted cell sorting. These effects were more profound when both, hyperoxia and CI, were used. Additionally, gene and protein expression of caspases 1, 3, 6, 7, and 9 were down-regulated significantly in MSCs preconditioned with hyperoxia, CI, or both, while the survival markers Akt1, NF-κB, and Bcl-2 were significantly increased in preconditioned MSCs. These changes ultimately resulted in a significant increase in MSC proliferation in hypoxic environment as determined by BrdU assays compared to MSCs without preconditioning. These effects may prove to be of great clinical significance when transplanting stem cells into the hypoxic myocardium of post-myocardial infarction patients in order to attenuate LV remodeling and improve LV function.

Original languageEnglish (US)
Pages (from-to)2612-2623
Number of pages12
JournalJournal of Cellular Biochemistry
Volume114
Issue number11
DOIs
StatePublished - Nov 1 2013

Fingerprint

Hyperoxia
Caspase Inhibitors
Cell proliferation
Caspases
Stem cells
Mesenchymal Stromal Cells
Myocardial Infarction
Cell Proliferation
Ventricular Remodeling
Stem Cells
Left Ventricular Function
Apoptosis
Assays
Caspase 1
Survival
Annexin A5
In Situ Nick-End Labeling
Left Ventricular Dysfunction
Bromodeoxyuridine
Cell- and Tissue-Based Therapy

Keywords

  • Apoptosis
  • Caspase Inhibitor
  • Hyperoxia
  • Hypoxia
  • Mesenchymal Stem Cells
  • Preconditioning

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Preconditioning mesenchymal stem cells with caspase inhibition and hyperoxia prior to hypoxia exposure increases cell proliferation. / Saini, Uksha; Gumina, Richard J; Wolfe, Brian; Kuppusamy, M. Lakshmi; Kuppusamy, Periannan; Boudoulas, Konstantinos Dean.

In: Journal of Cellular Biochemistry, Vol. 114, No. 11, 01.11.2013, p. 2612-2623.

Research output: Contribution to journalArticle

Saini, Uksha ; Gumina, Richard J ; Wolfe, Brian ; Kuppusamy, M. Lakshmi ; Kuppusamy, Periannan ; Boudoulas, Konstantinos Dean. / Preconditioning mesenchymal stem cells with caspase inhibition and hyperoxia prior to hypoxia exposure increases cell proliferation. In: Journal of Cellular Biochemistry. 2013 ; Vol. 114, No. 11. pp. 2612-2623.
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