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Using induced pluripotent stem cells (iPSC) to model human neuromuscular connectivity: promise or reality?

TitleUsing induced pluripotent stem cells (iPSC) to model human neuromuscular connectivity: promise or reality?
Publication TypeJournal Article
Year of Publication2012
AuthorsThomson SR, Wishart TM, Patani R, Chandran S, Gillingwater TH
JournalJ Anat
Date Published2012 Feb
KeywordsAnimals, Disease Models, Animal, Humans, Induced Pluripotent Stem Cells, Models, Biological, Motor Neuron Disease, Neuromuscular Junction, Synapses

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.

Alternate JournalJ. Anat.
PubMed ID22133357
PubMed Central IDPMC3275767
Grant List / / Wellcome Trust / United Kingdom