Servizio Comunitario di Informazione in materia di Ricerca e Sviluppo - CORDIS

Exhaustion of the human muscle organotypic stem cell with ageing; prognostic tool for human cell therapy

We investigated whether the lifelong consumption of the organotypic muscle stem cells, the satellite cells, might lead to their exhaustion in aged people. Human myogenic cells derived from donors aged 2-82 years and from biopsies of 3 children suffering from Duchenne Muscular Dystrophy (DMD) in which satellite cells are thought to suffer premature ageing, were implanted into immunincompetent mice.

The progeny of the grafted cells was quantified by structural features and by the amount of human DNA extractable from these muscles. When considering highly pure myogenic cell preparations, we observed an inverse relation between the donor's age and the proliferation capacity in vitro as well as in vivo with about 2 divisions of each satellite cell per 10 years of life. Myogenic cells from the oldest donors still grew human muscle tissue, indicating a lack of exhaustion even in aged donors in spite of a continual loss of growth capacity of satellite cells in the living muscle.

On the other hand, cell preparations with initially low or decreasing myogenicity during expansion in vitro showed completely different growth characteristics, e.g. increased proliferation capacity, longer telomeres and lower myogenicity of the tissue formed upon implantation. We suggest a "Desmin Factor" (DF) to predict myogenicity of the human tissue formed in vivo from the growth characteristics during expansion in vitro. This may serve as a prognostic tool in human trials.

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University of Bonn, Dept. of Physiology II
Wilhelmstr. 31
53111 Bonn
Germany
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