Developing three dimensional muscle nerve constructs
PhD Supervisor(s): Professor Mark Lewis and Dr Alexandra Stolzing
Major advances in the care of pregnant women and children, public health campaigns, safer environments and the introduction of advanced surgical and medical techniques has led to the population of many global nations living longer. The downside of this is that conditions that tend to manifest later in life are creating many emotional and economic difficulties. Amongst these conditions, the shadow of neurological disease looms large. Those diseases that affect the lower motor neurons often manifest themselves with debilitating effects on the musculature including weakness and atrophy. The link between the nervous system and the musculature is therefore key and this interaction occurs via the neuromuscular junction. Research in this area often uses rodents although there is an emerging tendency to return to primate use due to concerns over species specificity. So there is a clear need to develop interventions to treat or prevent such conditions as mentioned above. The major testing models are animals however this type of experimentation is not amenable to wide-scale screening and is subject to various issues of expense and regulation e.g. how can multiple agents be screened? What about combinations of pharmacological and non-pharmacological therapies e.g. exercise?
Our group has, over the past decade and more, been developing and refining biomimetic models of skeletal muscle (using regenerative medicine and tissue engineering principles) that can be simulated (exercised) in vitro. As part of the continual improvements, we have been working on recreating a neuromuscular junction by co-culturing the skeletal muscle with motor neurons. This work has been supported by 6 years of grant funding and is moving from non-human cell lines to human based systems. Most recently, we have been investigating the utility of human stem cells to generate the neural components as these can’t be harvested from living humans.
