Using induced pluripotent stem cells (iPSC) to model human neuromuscular connectivity: promise or reality?
Article first published online: 2 DEC 2011
© 2011 The Authors. Journal of Anatomy © 2011 Anatomical Society
Journal of Anatomy
Volume 220, Issue 2, pages 122–130, February 2012
How to Cite
Thomson, S. R., Wishart, T. M., Patani, R., Chandran, S. and Gillingwater, T. H. (2012), Using induced pluripotent stem cells (iPSC) to model human neuromuscular connectivity: promise or reality?. Journal of Anatomy, 220: 122–130. doi: 10.1111/j.1469-7580.2011.01459.x
- Issue published online: 5 JAN 2012
- Article first published online: 2 DEC 2011
- Accepted for publication 1 November 2011 Article published online 2 December 2011
- Amyotrophic lateral sclerosis;
- spinal muscular atrophy;
- neuromuscular junction;
- stem cells;
- in vitro model
Motor neuron diseases (MND) such as amyotrophic lateral sclerosis and spinal muscular atrophy are devastating, progressive and ultimately fatal diseases for which there are no effective treatments. Recent evidence from systematic studies of animal models and human patients suggests that the neuromuscular junction (NMJ) is an important early target in MND, demonstrating functional and structural abnormalities in advance of pathological changes occurring in the motor neuron cell body. The ability to study pathological changes occurring at the NMJ in humans is therefore likely to be important for furthering our understanding of disease pathogenesis, and also for designing and testing new therapeutics. However, there are many practical and technical reasons why it is not possible to visualise or record from NMJs in pre- and early-symptomatic MND patients in vivo. Other approaches are therefore required. The development of stem cell technologies has opened up the possibility of creating human NMJs in vitro, using pluripotent cells generated from healthy individuals and patients with MND. This review covers historical attempts to develop mature and functional NMJs in vitro, using co-cultures of muscle and nerve from animals, and discusses how recent developments in the generation and specification of human induced pluripotent stem cells provides an opportunity to build on these previous successes to recapitulate human neuromuscular connectivity in vitro.