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Title: Improved angiogenic response in pig heart following ischaemic injury using human skeletal myoblast simultaneously expressing VEGF165and angiopoietin-1
Authors: Ye, L. 
Sim, E.K.W. 
Haider, H.Kh. 
Jiang, S.
Tan, R.S.
Ge, R. 
Law, P.K.
Keywords: Angiogenesis
Gene therapy
Skeletal myoblast
Issue Date: 2007
Citation: Ye, L., Sim, E.K.W., Haider, H.Kh., Jiang, S., Tan, R.S., Ge, R., Law, P.K. (2007). Improved angiogenic response in pig heart following ischaemic injury using human skeletal myoblast simultaneously expressing VEGF165and angiopoietin-1. European Journal of Heart Failure 9 (1) : 15-22. ScholarBank@NUS Repository.
Abstract: 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 × 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. © 2006 European Society of Cardiology.
Source Title: European Journal of Heart Failure
ISSN: 13889842
DOI: 10.1016/j.ejheart.2006.04.008
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