Preconditioning enhances cell survival and differentiation of stem cells during transplantation in infarcted myocardium

Zeeshan Pasha, Yigang Wang, Riazuddin Sheikh, Dongsheng Zhang, Tiemin Zhao, Muhammad Ashraf

Research output: Contribution to journalArticle

233 Citations (Scopus)

Abstract

Aims: We hypothesized that preconditioning (PC) with stromal-derived factor 1 alpha (SDF-1) significantly enhances cell survival, proliferation, and engraftment of bone marrow-derived mesenchymal stem cells (MSCs) via SDF-1/CXCR4 signaling. Methods and results: MSCs were cultured and then incubated in medium for 60 min without SDF-1 (control group) or with SDF-1 0.05 μg/mL (SDF-1 group) or CXCR4-selective antagonist, AMD 3100 (AMD) (5 μg/mL, AMD group) or SDF-1 and AMD (0.05 μg/mL, 5 μg/mL, respectively, SDF-1+AMD group). MSCs were treated for 60 min, washed in normal medium, and then exposed to H 2O2 (100 μmol/L) for 60 min to determine the effects of various treatments on cell injury, viability, and proliferation. For in vivo studies, rats were grouped (n = 6) after left anterior descending coronary artery ligation to receive 20 μL Dulbecco's modified Eagle's medium without cells or with 5 × 105 non-preconditioned MSCs (control group), SDF-1 preconditioned MSCs (SDF-1 group), AMD (AMD group), or MSCs treated with SDF-1 plus AMD (SDF-1+AMD group). Heart function, infarct size, fibrosis, and MSC proliferation and differentiation in infarcted myocardium were determined after 4 weeks. In vitro data showed a marked increase in cell viability and proliferation following SDF-1 PC. In vivo data in preconditioned group showed a robust cell proliferation, reduction in infarct size and fibrosis, and significant improvement in cardiac function. Effects of SDF-1 PC were abrogated by CXCR4 antagonist. Conclusion: We conclude that PC with the chemokine SDF-1 suppresses MSCs apoptosis, enhances their survival, engraftment, and vascular density, and improves myocardial function via SDF/CXCR4 signaling. Chemokine PC is a novel approach for enhancing stem cell survival and regeneration of infarcted myocardium.

Original languageEnglish (US)
Pages (from-to)134-142
Number of pages9
JournalCardiovascular Research
Volume77
Issue number1
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

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Stem Cell Transplantation
Mesenchymal Stromal Cells
Cell Differentiation
Cell Survival
Myocardium
Cell Proliferation
Chemokines
Fibrosis
Control Groups
Eagles
Ligation
Blood Vessels
Regeneration
Coronary Vessels
Stem Cells
Bone Marrow
Apoptosis
Wounds and Injuries
actinomycin D1

Keywords

  • Apoptosis
  • Infarction
  • Myoangiogenesis
  • Preconditioning
  • Stromal-derived factor 1 alpha

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Preconditioning enhances cell survival and differentiation of stem cells during transplantation in infarcted myocardium. / Pasha, Zeeshan; Wang, Yigang; Sheikh, Riazuddin; Zhang, Dongsheng; Zhao, Tiemin; Ashraf, Muhammad.

In: Cardiovascular Research, Vol. 77, No. 1, 01.01.2008, p. 134-142.

Research output: Contribution to journalArticle

Pasha, Zeeshan ; Wang, Yigang ; Sheikh, Riazuddin ; Zhang, Dongsheng ; Zhao, Tiemin ; Ashraf, Muhammad. / Preconditioning enhances cell survival and differentiation of stem cells during transplantation in infarcted myocardium. In: Cardiovascular Research. 2008 ; Vol. 77, No. 1. pp. 134-142.
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AU - Zhao, Tiemin

AU - Ashraf, Muhammad

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AB - Aims: We hypothesized that preconditioning (PC) with stromal-derived factor 1 alpha (SDF-1) significantly enhances cell survival, proliferation, and engraftment of bone marrow-derived mesenchymal stem cells (MSCs) via SDF-1/CXCR4 signaling. Methods and results: MSCs were cultured and then incubated in medium for 60 min without SDF-1 (control group) or with SDF-1 0.05 μg/mL (SDF-1 group) or CXCR4-selective antagonist, AMD 3100 (AMD) (5 μg/mL, AMD group) or SDF-1 and AMD (0.05 μg/mL, 5 μg/mL, respectively, SDF-1+AMD group). MSCs were treated for 60 min, washed in normal medium, and then exposed to H 2O2 (100 μmol/L) for 60 min to determine the effects of various treatments on cell injury, viability, and proliferation. For in vivo studies, rats were grouped (n = 6) after left anterior descending coronary artery ligation to receive 20 μL Dulbecco's modified Eagle's medium without cells or with 5 × 105 non-preconditioned MSCs (control group), SDF-1 preconditioned MSCs (SDF-1 group), AMD (AMD group), or MSCs treated with SDF-1 plus AMD (SDF-1+AMD group). Heart function, infarct size, fibrosis, and MSC proliferation and differentiation in infarcted myocardium were determined after 4 weeks. In vitro data showed a marked increase in cell viability and proliferation following SDF-1 PC. In vivo data in preconditioned group showed a robust cell proliferation, reduction in infarct size and fibrosis, and significant improvement in cardiac function. Effects of SDF-1 PC were abrogated by CXCR4 antagonist. Conclusion: We conclude that PC with the chemokine SDF-1 suppresses MSCs apoptosis, enhances their survival, engraftment, and vascular density, and improves myocardial function via SDF/CXCR4 signaling. Chemokine PC is a novel approach for enhancing stem cell survival and regeneration of infarcted myocardium.

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