Angiogenic gene modification of skeletal muscle cells to compensate for ageing-induced decline in bioengineered functional muscle tissue.
OBJECTIVE
To explore the effects of ageing on the viability of bioengineered striated muscle tissue in vivo, and if this viability can be enhanced by concurrent neovascularization, as its utility for the treatment of stress urinary incontinence (SUI) might be reduced if muscle cells are derived from old patients.


METHODS
Myoblasts were obtained and expanded in culture from young (2 weeks), mature (3 months) and old (24 months) mice, and were engineered to express vascular endothelial growth factor (VEGF) to stimulate neovascularization. Myoblasts were injected subcutaneously into male nude mice and after 2 and 4 weeks, the engineered muscle tissues were harvested.


RESULTS
Bioengineered muscle tissues were formed in all groups, but the engineered muscles formed by myoblasts from old mice were smaller and less contractile. However, the bioengineered muscles expressing VEGF had a greater mass and better contractility in all age groups.


CONCLUSIONS
This pilot study showed that there was an age-related decline in the size and function of bioengineered muscle; however, there was an improvement in volume and function when the muscle cells were expressing VEGF.
Delo
Dawn M
DM
Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA.
Eberli
Daniel
D
Williams
J Koudy
JK
Andersson
Karl-Erik
KE
Atala
Anthony
A
Soker
Shay
S
D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D005260:Female; D005818:Genetic Engineering / Q000379:methods; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000502:physiology; D032448:Myoblasts, Skeletal / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D010865:Pilot Projects; D023822:Tissue Engineering / Q000379:methods; D014550:Urinary Incontinence, Stress / Q000209:etiology / Q000628:therapy; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A