Human VEGF165-myoblasts produce concomitant angiogenesis/myogenesis in the regenerative heart

Bioengineering the regenerative heart may provide a novel treatment for heart failure. On May 14, 2002, a 55-year-old man suffering from ischemic myocardial infarction received 25 injections carrying 465 million cGMP-produced pure myoblasts into his myocardium after coronary artery bypass grafting....

Full description

Saved in:
Bibliographic Details
Published in:Molecular and cellular biochemistry 2004-08, Vol.263 (1-2), p.173-178
Main Authors: Law, Peter K, Haider, Kh, Fang, G, Jiang, S, Chua, F, Lim, Y T, Sim, E
Format: Article
Language:English
Subjects:
Animals
Cardiomyocytes
Heart - physiology
Heart attacks
Heart failure
Humans
Lac Operon
Muscle Development
Myoblasts, Cardiac - metabolism
Myoblasts, Cardiac - transplantation
Myocardial infarction
Myocardium - metabolism
Myocardium - ultrastructure
Neovascularization, Physiologic
Regeneration - physiology
Swine
Transduction, Genetic
Transplantation, Heterologous
Vascular Endothelial Growth Factor A - genetics
Vascular Endothelial Growth Factor A - physiology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Bioengineering the regenerative heart may provide a novel treatment for heart failure. On May 14, 2002, a 55-year-old man suffering from ischemic myocardial infarction received 25 injections carrying 465 million cGMP-produced pure myoblasts into his myocardium after coronary artery bypass grafting. As on August 28, 2002, his EKG was normal and showed no arrhythmia. His ejection fraction increased by 13%. He no longer experienced shortness of breath and angina as he did before the treatment. Three myogenesis mechanisms were elucidated with 17 human/porcine xenografts using cyclosporine as immunosuppressant. Some myoblasts developed to become cardiomyocytes. Others transferred their nuclei into host cardiomyocytes through natural cell fusion. As yet others formed skeletal myofibers with satellite cells. De novo production of contractile filaments augmented the heart contractility. Human myoblasts transduced with VEGF165 gene produced six times more capillaries in porcine myocardium than in placebo. Xenograft rejection was not observed for up to 20 weeks despite cyclosporine discontinuation at 6 weeks. Pros and cons of autografts vs. allografts are compared to guide future development of heart cell therapy.
ISSN:0300-8177
1573-4919
DOI:10.1023/B:MCBI.0000041859.60354.f5