Skeletal Muscle Regeneration for Clinical Application

Abstract

Comprising nearly 50% of the human body [1] skeletal muscles compose the machinery that sets the body in movement. When well-trained, muscles have the capability to protect joints and bones from daily waste and trauma [2]. They hold an intrinsic protective mechanism against cancer formation and metastasis settling [3] and are at the same time the main energy reservoir of the body storing more than 80% of our glycogen reserve [4]. Hence, muscle tissue is associated to several functions and networks with different parts of the body. It is composed of muscle fibers, the contractile units, which are bound together by connective tissue. Most importantly, skeletal muscles display an astonishing regenerative capacity [5]. Due to resident stem cells, one week after severe trauma new myotubes are already being formed, and within 28 days after trauma muscle regeneration is almost complete [6]. These intrinsic features turn the skeletal muscle into a very interesting topic of study in regenerative medicine. Taking advantage of the regenerative potential of stem and precursor cells, skeletal muscle is con‐ stantly renewed in response to injury, damage or aging. It is this natural process that research‐ ers are about to harness in order to help patients with many muscle diseases and diseases that causes weakness or destruction of the muscle - for instance stress urinary incontinence (SUI), muscular dystrophy. In this chapter, the focus will be on the regeneration of the skeletal muscle and especially in the case of incontinence. Urinary incontinence is the involuntary loss of urine and is a major medical problem affecting millions of people worldwide. It impairs the quality of life of patients and involves high healthcare costs. The main reason provoking SUI is the damage of the sphincter muscle due to childbirth, surgical treatments (as prostatectomy) or as an effect of aging. Current treatment encompasses behavioral training, pelvic floor exercising, drugs, medical devices and surgery. Unfortunately, all these options permit only limited recovery: short-term relief and are often accompanied with complications. The ultimate goal will be to prevent disease progression and to restore the tissue and its functions. Stem cell therapy as a treatment for skeletal muscle diseases is becoming a reality and it represents a promising alternative for muscle regeneration and for treating SUI in a more complete and definitive manner. In this chapter, the homeostasis and maintenance of skeletal muscle is explained in order to understand the basis behind muscle regeneration. As different types of stem cells have been demonstrated to form fibers and to develop into skeletal muscle, cell sources for a muscle cell therapy is discussed. Some of them have also been applied successfully in preclinical and clinical studies that are going to be described. Finally, we are going to highlight the parts important for the translational effort into clinics including biomaterials, cell delivery, imaging, regulatory affairs, and manufacturing.