© 2006 European Society of Cardiology
Improved angiogenic response in pig heart following ischaemic injury using human skeletal myoblast simultaneously expressing VEGF165 and angiopoietin-1
a Department of Surgery National University of Singapore-119074, Singapore
b National University Medical Institute National University of Singapore-117597, Singapore
c National Heart Centre, Singapore General Hospital Singapore
d Department of Biological Sciences, National University of Singapore Singapore
e Cell Therapy Research Foundation Memphis TN 38117-7126, USA
* Corresponding author. Department of Pathology and Laboratory Medicine, Medical Science Building, University of Cincinnati, Cincinnati OH 45220. E-mail addresses: haiderkh{at}UCMAIL.UC.edu, khhaider{at}hotmail.com
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Abstract |
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Objective: To achieve angiogenic interaction between VEGF165 and angiopoietin-1 (Ang-1) using a novel adenoviral bicistronic vector (Ad-Bic) encoding the two factors and delivered ex vivo using sex-mismatched human skeletal myoblasts.
Methods and results: A myocardial infarction model was developed in 29 female pigs; randomised into four groups: DMEM (group-1, n=6); Adenovirus null (Ad-null) vector-myoblast (group-2, n=5); Ad-Ang-1 myoblast (group 3, n=7) and Ad-Bic-myoblast (group-4, n=11). Three weeks later, 5 ml DMEM without myoblasts or containing 3 x 108 myoblasts carrying lac-z gene and transduced with Ad-null, Ad-Ang-1 or Ad-Bic were injected intra-myocardially in and around the infarct. 2D-echocardiography and fluorescent microsphere studies 6- and 12-weeks post-treatment revealed significantly improved cardiac performance and regional blood flow in groups 3 and 4. Histological studies and Y-chromosome analysis revealed extensive survival of lac-z positive myoblasts staining positive for human proteins in the pig heart. ELISA, immunostaining and RT-PCR revealed that Ad-Bic transduced myoblasts concomitantly but transiently expressed hVEGF165 and Ang-1 both in vitro and in vivo. Double fluorescent immunostaining of the tissue sections for vWFactor-III and smooth muscle actin showed significantly higher vascular density of mature blood vessels per low power microscopic field in groups 3 and 4 at 6- and 12-weeks.
Conclusion: Our combined approach led to enhanced angiogenesis with a greater percentage of functionally mature blood vessels in a porcine heart.
Key Words: Angiogenesis • Gene therapy • Infarction • Skeletal myoblast
Received June 14, 2005; Revised November 28, 2005; Accepted April 10, 2006
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  E. K. Sim, L. Ye, and H. K. Haider New Strategy for Cardiac Repair: Genetically Modified Skeletal Myoblasts Asian Cardiovasc Thorac Ann, June 1, 2007; 15(3): 183 - 184. [Full Text] [PDF]
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