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

102 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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