Ex vivo delivered stromal cell-derived factor-1α promotes stem cell homing and induces angiomyogenesis in the infarcted myocardium

I. Elmadbouh, Husnain Kh Haider, Shujia Jiang, Niagara Muhammad Idris, Gang Lu, Muhammad Ashraf

Research output: Contribution to journalArticle

152 Citations (Scopus)

Abstract

We aimed to optimize non-viral transfection of human stromal cell derived factor (SDF-1α) gene into skeletal myoblasts (SkM) and, transplant these cells to establish transient SDF-1α gradient to favor extra-cardiac stem cell translocation into infarcted heart. Optimized conditions for transfection of SDF-1α gene into syngenic SkM were achieved using FuGene™6/phSDF-1α (3:2v/w, 4 h transfection) with 125 μM ZnCl2 (p < 0.001). After characterization for transgene overexpression by immunostaining, ELISA and PCR, the cells were transplanted in female rat model of myocardial infarction. Thirty-six rats were grouped (n = 12/group) to receive 70 μl DMEM without cells (group-1) or containing 1.5 × 106 non-transfected (group-2) or SDF-1α transfected SkM (group-3). On day 4 post-transplantation (in 4 animals/group), marked expression of SDF-1α/sry-gene (p = 0.003), total Akt, phospho-Akt and Bcl2 was observed in group-3. The number of CD31+, C-kit+ and CD34+ cells was highest in group-3 hearts (p < 0.01). Blood vessel density in group-3 was higher in both scar and peri-scar regions (p < 0.001) as compared with other groups. Echocardiography showed improved indices of left ventricle contractile function and remodeling in group-3 (p < 0.05) as compared with groups-1 and -2. We conclude that ex vivo SDF-1α transgene delivery promotes stem and progenitor cell migration to the heart, activates cell survival signaling and enhances angiomyogenesis in the infarcted heart.

Original languageEnglish (US)
Pages (from-to)792-803
Number of pages12
JournalJournal of molecular and cellular cardiology
Volume42
Issue number4
DOIs
StatePublished - Apr 1 2007

Fingerprint

Chemokine CXCL12
Skeletal Myoblasts
Myocardium
Stem Cells
Transfection
Transgenes
Cicatrix
sry Genes
Genes
Heart Ventricles
Cell Movement
Blood Vessels
Echocardiography
Cell Survival
Transplantation
Enzyme-Linked Immunosorbent Assay
Myocardial Infarction
Transplants
Polymerase Chain Reaction

Keywords

  • Angiogenesis
  • Apoptosis
  • Chemokine
  • Myoblast
  • Myocardial infarction
  • Myogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Ex vivo delivered stromal cell-derived factor-1α promotes stem cell homing and induces angiomyogenesis in the infarcted myocardium. / Elmadbouh, I.; Haider, Husnain Kh; Jiang, Shujia; Idris, Niagara Muhammad; Lu, Gang; Ashraf, Muhammad.

In: Journal of molecular and cellular cardiology, Vol. 42, No. 4, 01.04.2007, p. 792-803.

Research output: Contribution to journalArticle

Elmadbouh, I. ; Haider, Husnain Kh ; Jiang, Shujia ; Idris, Niagara Muhammad ; Lu, Gang ; Ashraf, Muhammad. / Ex vivo delivered stromal cell-derived factor-1α promotes stem cell homing and induces angiomyogenesis in the infarcted myocardium. In: Journal of molecular and cellular cardiology. 2007 ; Vol. 42, No. 4. pp. 792-803.
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AU - Haider, Husnain Kh

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AU - Idris, Niagara Muhammad

AU - Lu, Gang

AU - Ashraf, Muhammad

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AB - We aimed to optimize non-viral transfection of human stromal cell derived factor (SDF-1α) gene into skeletal myoblasts (SkM) and, transplant these cells to establish transient SDF-1α gradient to favor extra-cardiac stem cell translocation into infarcted heart. Optimized conditions for transfection of SDF-1α gene into syngenic SkM were achieved using FuGene™6/phSDF-1α (3:2v/w, 4 h transfection) with 125 μM ZnCl2 (p < 0.001). After characterization for transgene overexpression by immunostaining, ELISA and PCR, the cells were transplanted in female rat model of myocardial infarction. Thirty-six rats were grouped (n = 12/group) to receive 70 μl DMEM without cells (group-1) or containing 1.5 × 106 non-transfected (group-2) or SDF-1α transfected SkM (group-3). On day 4 post-transplantation (in 4 animals/group), marked expression of SDF-1α/sry-gene (p = 0.003), total Akt, phospho-Akt and Bcl2 was observed in group-3. The number of CD31+, C-kit+ and CD34+ cells was highest in group-3 hearts (p < 0.01). Blood vessel density in group-3 was higher in both scar and peri-scar regions (p < 0.001) as compared with other groups. Echocardiography showed improved indices of left ventricle contractile function and remodeling in group-3 (p < 0.05) as compared with groups-1 and -2. We conclude that ex vivo SDF-1α transgene delivery promotes stem and progenitor cell migration to the heart, activates cell survival signaling and enhances angiomyogenesis in the infarcted heart.

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KW - Myocardial infarction

KW - Myogenesis

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