Angiogenic gene modification of skeletal muscle cells to compensate for ageing-induced decline in bioengineered functional muscle tissue

BJU Int. 2008 Sep;102(7):878-84. doi: 10.1111/j.1464-410X.2008.07750.x. Epub 2008 May 16.

Abstract

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.

Materials and 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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Aging / physiology*
  • Animals
  • Female
  • Genetic Engineering / methods
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Muscle, Skeletal / blood supply*
  • Muscle, Skeletal / physiology
  • Myoblasts, Skeletal / physiology*
  • Neovascularization, Physiologic / genetics
  • Neovascularization, Physiologic / physiology*
  • Pilot Projects
  • Tissue Engineering / methods
  • Urinary Incontinence, Stress / etiology
  • Urinary Incontinence, Stress / therapy
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Vascular Endothelial Growth Factor A