Stem cell therapy in muscle degeneration

Abstract

Skeletal muscle is one of the largest tissues in humans, reaching around 38% of the body weight for men and 30% for women (Janssen I, et al, J Appl Physiol 89(1):81-88, 1985/2000). Muscle tissue finely regulates essential body movements, including respiration, equilibrium maintenance and ambulation. In addition, it controls body temperature and energy balance and restores blood glucose levels. Genetic or acquired alterations in these enzymes can lead to metabolic syndromes (McArdle’s syndrome (Vorgerd M, Neurotherapeutics 5(4):579-582 2008) or diabetes (DeFronzo RA, Tripathy D, Diabetes Care 32(Suppl 2):S157- S163 2009). Muscle tissue is originated during embryo development, from the fusion of mesoderm progenitors. During the neonatal and early juvenile period, even if the myofibre number remains constant, new postnatal multipotent cells, called satellite cells (SCs), can fuse and increase the number of nuclei per fibre (Biressi S, et al, Dev Biol 379(2):195-207, 2013). Adult skeletal muscle is organised in long fibres generated from the fusion of single cells into a unique syncytium able to collect thousands of nuclei and of myofibrils. Each myofibril contains multiple sarcomeres, formed by actin and myosin filaments to generate contraction and develop force. High heterogeneity is present among single fibres, including slow-contracting fatigue-resisting type I fibres (also known as slow-twitch, tonic or simply slow fibres) and fast-contracting fatigue-unresisting type II fibres (fasttwitch, phasic or fast fibres). To exert a good performance, the expression of specific contractile proteins and metabolic enzymes is necessary together with a regular connection to a single motor neuron and an efficient vascularisation. Myotendinous junctions connect myofibres from one side and bones in the skeleton on the other side, allowing transmission of contractions to other muscles. Daily wear and tear or excessive load and damage of the fibre integrity activate SCs that undergo fusion. The highly orchestrated process has been thoroughly studied. Nevertheless, understanding the role of local and circulating cell types in adult myogenesis still remains a matter of discussion (Relaix F, Zammit PS, Development 139(16):2845- 2856, 2012). In this chapter after introducing the biological events occurring in acute and chronic skeletal muscle damages, cell and gene therapy approaches are considered as novel tools to preserve muscle function.