Combining pharmacological mobilization with intramyocardial delivery of bone marrow cells over-expressing VEGF is more effective for cardiac repair

Yigang Wang, Husnain K. Haider, Nauman Ahmad, Meifeng Xu, Ruowen Ge, Muhammad Ashraf

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

We postulated that combining cell based hVEGF165 gene delivery with cytokine-induced mobilization of bone marrow cells (BMC) may give better prognosis in an infarcted heart. Forty-eight myoabalated female C57BL/6J mice (20-25 g) received 1 × 106 BMC from transgenic GFP+ male mice. One month later, acute myocardial infarction (MI) model was developed by coronary artery ligation. Animals were grouped (N = 12) to receive intramyocardial injections of 10 μl DMEM without cells (group 1; group 2) or with 1 × 105 mesenchymal stem cells (MSC) over-expressing hVEGF165 (group 3; group 4). The animals received either cytokine therapy (group 2 and 4) or saline solution (group 1 and 3) for 7 days after MI. Hemodynamic data were obtained 4 weeks after MI using Millar's P-V system and cardiac tissue was harvested for immunohistological studies. We observed regeneration and extensive survival of BMC in and around the infarcted myocardium in groups 3 and 4. Blood vessel density was markedly enhanced in group 4 as compared with groups 1 and 2 in peri-infarct area. Fibrotic area was significantly reduced with improved LV-contractile function in group 2 and 4. LV-systolic and diastolic functions were well-preserved in group 4 as indicated by +dP/dt, -dP/dt and Tau (glantz). We therefore conclude that transplantation of MSC overexpressing VEGF combined with cytokine induced BMC mobilization is superior to either of the monotherapy approach for angiomyogenesis and LV-function recovery.

Original languageEnglish (US)
Pages (from-to)736-745
Number of pages10
JournalJournal of molecular and cellular cardiology
Volume40
Issue number5
DOIs
StatePublished - May 1 2006
Externally publishedYes

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Bone Marrow Cells
Vascular Endothelial Growth Factor A
Bone Marrow
Pharmacology
Myocardial Infarction
Cytokines
Mesenchymal Stem Cell Transplantation
Recovery of Function
Group Psychotherapy
Mesenchymal Stromal Cells
Inbred C57BL Mouse
Sodium Chloride
Ligation
Blood Vessels
Regeneration
Coronary Vessels
Myocardium
Hemodynamics
Injections
Genes

Keywords

  • Angiogenesis
  • Bone marrow stem cells
  • Cytokines
  • Heart infarction
  • Myocyte regeneration

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Combining pharmacological mobilization with intramyocardial delivery of bone marrow cells over-expressing VEGF is more effective for cardiac repair. / Wang, Yigang; Haider, Husnain K.; Ahmad, Nauman; Xu, Meifeng; Ge, Ruowen; Ashraf, Muhammad.

In: Journal of molecular and cellular cardiology, Vol. 40, No. 5, 01.05.2006, p. 736-745.

Research output: Contribution to journalArticle

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