> Myostatin – the factor that makes all the difference (Christophe Marcelle, France) > Duchenne muscular dystrophy – towards the first clinical trial by mesoangioblasts in humans (Giulio Cossu, Italy)

Myostatin – the factor that makes all the difference (Christophe Marcelle, France)

Devoted to muscle stem cells, the first day of the Myology 2008 congress opened with the contribution of researchers expert in the field of muscle development, in particular Christophe Marcelle (Developmental Biology Institute at Marseille-Luminy), one of the coordinators of the Myores network. This European network of excellence is financed by the European Union with the AFM as one of its partners. It is dedicated to the study of normal and pathological muscle development through multi-organism approaches. It brings together the best European research teams with the aim of speeding up fundamental research and promoting clinical applications for neuromuscular diseases.
Professor Christophe Marcelle presented the latest advances of his team concerning muscle development in the embryo. The researchers have identified a population of muscle progenitors which participate in the growth of all the skeletal muscles of the embryo and foetus. Interestingly, these embryonic progenitor cells have the same origin as satellite cells (adult muscle stem cells). These progenitor cells then proliferate and differentiate to give normal muscle. Muscle growth is determined by progenitor cells which divide and those which differentiate. What are the factors determining whether a cell will divide or differentiate? In 2007 Christophe Marcelle’s team demonstrated that the Notch factor was involved in both the proliferation and differentiation of embryonic muscle progenitor cells. This time the researchers have analysed the role of myostatin in this process and shown that this protein promotes progenitor cells towards differentiation. Thus, long-term over-activation of myostatin disturbs the balance of muscle growth and causes excessive and pathological differentiation. The involvement of myostatin in the differentiation embryonic muscle progenitors brings to light the role of this protein in muscle development and its potential therapeutic use.
For further information: www.myores.org

Duchenne muscular dystrophy – towards the first clinical trial by mesoangioblasts in humans (Giulio Cossu, Italy)

Adult human mesoangioblasts (taken from muscle biopsies) were recently isolated and multiplied in vitro. They correspond to a subset of pericytes (cells located in the blood vessel walls) with the capacity to develop spontaneously and highly effectively into skeletal muscle. This is an endogenous programme proper to skeletal muscle cells which contributes to the formation of skeletal muscle fibres and cardiomyocytes in normal subjects after birth.
Giulo Cossu’s team (Italy) has shown that intra-arterial injection of mesangioblasts from healthy dogs leads to a histological improvement in the dystrophic dog. Dystrophin was expressed in 5 to 90% of muscle fibres.
Following these encouraging results, the researchers are preparing a phase I/II clinical trial on Duchenne muscular dystrophy patients. The main objective of this trial is to test the long- and short-term safety of intra-arterial mesangioblast injection (allotransplantation using cell donors from an HLA-typed donor). Among the problems to be solved are: long-term immunosuppressor treatment and the impossibility to include older patients. The team hopes to solve these problems in the future by using various methods: autologous injection, mesangioblast immortalisation and an artificial chromosome containing the whole-gene of full-length dystrophin.