Combined cord blood stem cells and gene therapy enhances angiogenesis and improves cardiac performance in mouse after acute myocardial infarction

H. K. Chen, H. F. Hung, Kou-Gi Shyu, B. W. Wang, J. R. Sheu, Y. J. Liang, C. C. Chang, P. Kuan

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Background: Gene and stem cell therapies hold promise for the treatment of ischaemic cardiovascular disease. However, combined stem cell and angiogenic growth factor gene therapy for acute ischaemic myocardium has not been previously reported. This study hypothesized that combined stem cell and gene therapy would not only augment new vessels formation but also improve myocardial function in acute ischaemic myocardium. Materials and methods: Human angiopoietin-1 (Ang1) cDNA and VEGF165 cDNA were ligated into AAV vector. The purified CD34+ cells were obtained from human umbilical cord blood samples. Cord blood CD34+ cells were transduced with AAV vector encoding either the human Ang1 (AAV-Ang1) or VEGF165 (AAV-VEGF) cDNA alone, or both (AAV-Ang1 plus VEGF). Immediately after ligation of the left anterior descending coronary artery in male SCID mice, culture-expanded CD34+ cells transduced with AAV-Ang1, AAV-VEGF or AAV-Ang1 plus VEGF were injected intramyocardially at the left anterior free wall. Result: Western blot showed that Ang1 and VEGF protein expressions were enhanced in the CD34+ cells transduced with AAV-Ang1 and AAV-VEGF, respectively. Infarct size significantly decreased and capillary density significantly increased after treatment with CD34+/AAV-Ang1 plus VEGF when compared with treatment by CD34+ only. Combined therapy with CD34+ and AAV-Ang1, CD34+ and AAV-VEGF, CD34+ and AAV-Ang1 plus VEGF, all showed significantly higher cardiac performance in echocardiography than the therapy with CD34+ alone 4 weeks after myocardial infarction. Conclusions: Combined therapy with human umbilical cord blood CD34+ cells and both Ang1 and VEGF genes reduced infarct size, attenuated the progression of cardiac dysfunction and increased capillary density in acute myocardial infarction in mice.

Original languageEnglish
Pages (from-to)677-686
Number of pages10
JournalEuropean Journal of Clinical Investigation
Volume35
Issue number11
DOIs
Publication statusPublished - Nov 2005

Fingerprint

Angiopoietin-1
Gene therapy
Cell- and Tissue-Based Therapy
Stem cells
Fetal Blood
Genetic Therapy
Blood Cells
Blood
Stem Cells
Myocardial Infarction
Vascular Endothelial Growth Factor A
Complementary DNA
Myocardium
Therapeutics
Genes
Echocardiography
SCID Mice
Angiogenesis Inducing Agents
Ligation
Intercellular Signaling Peptides and Proteins

Keywords

  • Acute myocardial infarction
  • Angiogenesis
  • Angiopoietin-1
  • Cell therapy
  • Vascular endothelial growth factor
  • Vasculogenesis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Combined cord blood stem cells and gene therapy enhances angiogenesis and improves cardiac performance in mouse after acute myocardial infarction. / Chen, H. K.; Hung, H. F.; Shyu, Kou-Gi; Wang, B. W.; Sheu, J. R.; Liang, Y. J.; Chang, C. C.; Kuan, P.

In: European Journal of Clinical Investigation, Vol. 35, No. 11, 11.2005, p. 677-686.

Research output: Contribution to journalArticle

Chen, H. K. ; Hung, H. F. ; Shyu, Kou-Gi ; Wang, B. W. ; Sheu, J. R. ; Liang, Y. J. ; Chang, C. C. ; Kuan, P. / Combined cord blood stem cells and gene therapy enhances angiogenesis and improves cardiac performance in mouse after acute myocardial infarction. In: European Journal of Clinical Investigation. 2005 ; Vol. 35, No. 11. pp. 677-686.
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T1 - Combined cord blood stem cells and gene therapy enhances angiogenesis and improves cardiac performance in mouse after acute myocardial infarction

AU - Chen, H. K.

AU - Hung, H. F.

AU - Shyu, Kou-Gi

AU - Wang, B. W.

AU - Sheu, J. R.

AU - Liang, Y. J.

AU - Chang, C. C.

AU - Kuan, P.

PY - 2005/11

Y1 - 2005/11

N2 - Background: Gene and stem cell therapies hold promise for the treatment of ischaemic cardiovascular disease. However, combined stem cell and angiogenic growth factor gene therapy for acute ischaemic myocardium has not been previously reported. This study hypothesized that combined stem cell and gene therapy would not only augment new vessels formation but also improve myocardial function in acute ischaemic myocardium. Materials and methods: Human angiopoietin-1 (Ang1) cDNA and VEGF165 cDNA were ligated into AAV vector. The purified CD34+ cells were obtained from human umbilical cord blood samples. Cord blood CD34+ cells were transduced with AAV vector encoding either the human Ang1 (AAV-Ang1) or VEGF165 (AAV-VEGF) cDNA alone, or both (AAV-Ang1 plus VEGF). Immediately after ligation of the left anterior descending coronary artery in male SCID mice, culture-expanded CD34+ cells transduced with AAV-Ang1, AAV-VEGF or AAV-Ang1 plus VEGF were injected intramyocardially at the left anterior free wall. Result: Western blot showed that Ang1 and VEGF protein expressions were enhanced in the CD34+ cells transduced with AAV-Ang1 and AAV-VEGF, respectively. Infarct size significantly decreased and capillary density significantly increased after treatment with CD34+/AAV-Ang1 plus VEGF when compared with treatment by CD34+ only. Combined therapy with CD34+ and AAV-Ang1, CD34+ and AAV-VEGF, CD34+ and AAV-Ang1 plus VEGF, all showed significantly higher cardiac performance in echocardiography than the therapy with CD34+ alone 4 weeks after myocardial infarction. Conclusions: Combined therapy with human umbilical cord blood CD34+ cells and both Ang1 and VEGF genes reduced infarct size, attenuated the progression of cardiac dysfunction and increased capillary density in acute myocardial infarction in mice.

AB - Background: Gene and stem cell therapies hold promise for the treatment of ischaemic cardiovascular disease. However, combined stem cell and angiogenic growth factor gene therapy for acute ischaemic myocardium has not been previously reported. This study hypothesized that combined stem cell and gene therapy would not only augment new vessels formation but also improve myocardial function in acute ischaemic myocardium. Materials and methods: Human angiopoietin-1 (Ang1) cDNA and VEGF165 cDNA were ligated into AAV vector. The purified CD34+ cells were obtained from human umbilical cord blood samples. Cord blood CD34+ cells were transduced with AAV vector encoding either the human Ang1 (AAV-Ang1) or VEGF165 (AAV-VEGF) cDNA alone, or both (AAV-Ang1 plus VEGF). Immediately after ligation of the left anterior descending coronary artery in male SCID mice, culture-expanded CD34+ cells transduced with AAV-Ang1, AAV-VEGF or AAV-Ang1 plus VEGF were injected intramyocardially at the left anterior free wall. Result: Western blot showed that Ang1 and VEGF protein expressions were enhanced in the CD34+ cells transduced with AAV-Ang1 and AAV-VEGF, respectively. Infarct size significantly decreased and capillary density significantly increased after treatment with CD34+/AAV-Ang1 plus VEGF when compared with treatment by CD34+ only. Combined therapy with CD34+ and AAV-Ang1, CD34+ and AAV-VEGF, CD34+ and AAV-Ang1 plus VEGF, all showed significantly higher cardiac performance in echocardiography than the therapy with CD34+ alone 4 weeks after myocardial infarction. Conclusions: Combined therapy with human umbilical cord blood CD34+ cells and both Ang1 and VEGF genes reduced infarct size, attenuated the progression of cardiac dysfunction and increased capillary density in acute myocardial infarction in mice.

KW - Acute myocardial infarction

KW - Angiogenesis

KW - Angiopoietin-1

KW - Cell therapy

KW - Vascular endothelial growth factor

KW - Vasculogenesis

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