An in vitro model to replace animal testing of muscle physiology and function

骨骼肌是驱动我们的运动、姿势和呼吸的马达，使它们成为生命所必需的。老年人骨骼肌功能的丧失和慢性病的结果是跌倒和降低生活质量和寿命的主要原因。骨骼肌在新陈代谢中也起着至关重要的作用。肌肉代谢功能的丧失会导致和/或加剧一些慢性疾病，包括心脏病、高血压、肥胖、糖尿病、癌症、抑郁症和骨质疏松症。因此，大量的时间和金钱被投入到研究骨骼肌上。除了人类的投资，每年有超过50万只动物被用于研究肌肉的生理和功能如何适应疾病、基因、运动和药物。因此，创造一种研究肌肉生理和功能的替代方法，不仅可以减少用于这一目的的动物数量，还可以提高人类的生命质量和寿命。我们最近设计了一个肌肉模型，有可能实现这一点。为了进一步发展我们的模型并测试其作为动物研究替代品的有效性，这项提议着眼于：i)从永生细胞中设计肌肉，从而不再需要动物捐赠者；ii)在我们设计的肌肉和我们的实验机器之间建立一个接口；iii)创造新的机器，使我们能够更好地模拟运动和生长，并且可以商业化开发，以便其他人可以以合理的成本做类似的实验；以及iv)比较在工程肌肉中对模拟运动的反应是否与动物对运动的反应相似。

Skeletal muscles are the motors that drive our movement, posture and breathing making them essential to life. The loss of skeletal muscle function in the elderly and as a result of chronic disease is a major cause of falls and decreases quality of life and lifespan. Skeletal muscle also plays an essential function in metabolism. Loss of muscle metabolic function can cause and/or exacerbate a number of chronic diseases, including heart disease, high blood pressure, obesity, diabetes, cancer, depression, and osteoporosis. As a result, a lot of time and money is invested in studying skeletal muscle. Beyond the human investment, every year over 500,000 animals are used to study how the physiology and function of muscle adapts to disease, genes, exercise, and drugs. Therefore, creating an alternative method for the study of muscle physiology and function could not only reduce the number of animals used for this purpose but could improve the quality and length of human lives as well. We have recently engineered a model of a muscle that has the potential to achieve this. In order to further develop our model and test its usefulness as a replacement for animal studies, this proposal looks to: i) engineer muscle from immortal cells so that animal donors are no longer required; ii) create an interface between our engineered muscle and our experimental machines; iii) create new machines that would allow us to better mimic exercise and growth and that could be developed commercially so that others could do similar experiments at a reasonable cost; and iv) compare whether the response to simulated exercise in engineered muscles is similar to the response of an animal to exercise.