Sabatelli 2011 J Cell Physiol
|Sabatelli P, Palma E, Angelin A, Squarzoni S, Urciuolo A, Pellegrini C, Tiepolo T, Bonaldo P, Gualandi F, Merlini L, Bernardi P, Maraldi NM (2011) Critical evaluation of the use of cell cultures for inclusion in clinical trials of patients affected by Collagen VI myopathies. J Cell Physiol DOI: 10.1002/jcp.23039.|
Abstract: Collagen VI myopathies (Ullrich Congenital Muscular Dystrophy (UCMD), Bethlem Myopathy (BM) and Myosclerosis Myopathy) share a common pathogenesis, i.e. mitochondrial dysfunction due to deregulation of the permeability transition pore (PTP). This effect was first identified in the Col6a1-/- mouse model and then in muscle cell cultures from UCMD and BM patients; the normalizing effect of cyclosporin A (CsA) confirmed the pathogenic role of PTP opening. In order to determine whether mitochondrial performance can be used as a criterion for inclusion in clinical trials and as an outcome measure of the patient response to therapy, it is mandatory to establish whether mitochondrial dysfunction is conserved in primary cell cultures from UCMD and BM patients. In this study we report evidence that mitochondrial dysfunction and the consequent increase of apoptotic rate can be detected not only, as previously reported, in muscle, but also in fibroblast cell cultures established from muscle biopsies of collagen VI-related myopathic patients. However, the mitochondrial phenotype is no longer maintained after 9 passages in culture. These data demonstrate that the dire consequences of mitochondrial dysfunction are not limited to myogenic cells, and that this parameter can be used as a suitable diagnostic criterion, provided that the cell culture conditions are carefully established.
• Keywords: Latent mitochondrial dysfunction
Organism: Human, Mouse Tissue;cell: Skeletal muscle, Fibroblast Preparation: Intact cells
Latent mitochondrial dysfunction