Muscle fibrosis is accentuated by the partial loss of the identity and functionality of muscle cells

Most of the tissues in the adult human body have the ability to regenerate themselves in the event of damage or injury. But each time this regeneration takes place, it puts the maintenance of the identity (memory) of the cells of this tissue to the test. A process of cellular plasticity has been identified, that changes the phenotype of muscle cells causing dystrophy.

Duchenne Muscular Dystrophy (DMD) is a rare and unfortunately fatal degenerative disease in which the lack of a critical protein for the functioning of muscle fibres, dystrophin, gives rise to successive cycles of muscle degeneration/regeneration.

In patients with DMD the regenerative capacity of skeletal muscle gradually declines and the muscle is substituted by fibrotic tissue that prevents the function of muscles of vital importance such as the diaphragm and the heart.

A study published on 14 May in Stem Cell Reports by the group led by Pura Muñoz-Cánoves, ICREA research professor and head of the Cell Biology Unit of the Department of Experimental and Health Sciences (CEXS) at Pompeu Fabra University and a member of CIBERNED, has demonstrated the existence of cells in dystrophic muscle that gain plasticity, preventing them from maintaining their original cell identity causing muscle fibrosis.

As Patrizia Pessina, first author of the study points out, "we knew from earlier work by other groups that, in the initial stages of the disease, fibrosis is mainly due to the mobilization of cells with fibrotic capacity to the muscles".

Now the work carried out by the group led by Muñoz-Cánoves, "proves for the first time that in advanced stages of the disease, the process of fibrosis is aggravated by partial loss of the identity and functionality of the muscle and vascular cells and immune infiltrates", explains Pessina.

For people with DMD the consequences of these deficiencies are disastrous for muscle regeneration as they affect the muscle in two different ways; on the one hand through the absence of muscle and vascular cells needed to maintain the tissue, and on the other, bringing about the appearance of fibrosis-producing cells that accelerate deterioration.

Factor identified whose inhibition improves the disease

Another contribution of the work is that it identifies the existing relationship between the gain in cell plasticity and increased fibrosis in patients with DMD with an increase of the TGF-beta factor, and an intermediate multipotent state.

For this reason, the authors believe that the results obtained by pharmacologically inhibiting this pro-fibrotic factor in a murine model for DMD are encouraging, since it involves a reduction in fibrosis and an improvement of the muscle's regenerative capacity.

Reference work:

Patrizia Pessina, Yacine Kharraz, Mercè Jardí, So-ichiro Fukada, Antonio L. Serrano, Eusebio Perdiguero and Pura Muñoz-Cánoves, (2015), "Fibrogenic cell plasticity blunts tissue regeneration and aggravates muscular dystrophy", Stem Cell Reports, 14 May.