This proposal represents the synergistic opportunity between two currently independently funded NC3Rs grants. Both of these NC3Rs funded projects have shown independent impact progress and we now propose to synergistically exploit this progress to refine a test bed that will completely replace animal testing for neuromuscular effectors. Using techniques and approaches from the world of tissue engineering, we have successfully created skeletal muscle in the laboratory that can be stimulated in a variety of different ways—human constructs have also been created. We have also been able to co-culture these constructs with motor neurons and have increasing evidence of interactions between the cell types. One of the ambitions for this work was to develop a situation where appropriate cell lines could be developed that would remove the need for animal tissues altogether; this proposal does not explicitly seek to achieve that aim although it could be a subject of future grants. The limit to this ambition was the fact that the motor neuron component required animal tissues but, through NC3Rs networking sessions, we have identified a fellow grant-holder who has been funded to generate neuronal cells from human stem cells. The current project therefore is a direct continuation of both projects where the use for animals is totally removed.
Player DJ, Martin NR, Passey SL, Sharples AP, Mudera V, Lewis MP (2014). Acute mechanical overload increases IGF-I and MMP-9 mRNA in 3D tissue-engineered skeletal muscle. Biotechnol Lett 36(5): 1113-24. doi: 10.1007/s10529-014-1464-y.
Principal investigatorProfessor Mark Lewis
Co-InvestigatorDr Eric Hill
Dr Vivek Mudera