Critical Evaluation of the Use of Cell Cultures for Inclusion in Clinical Trials of Patients Affected by Collagen VI Myopathies
Autor: | Paolo Bonaldo, Elena Palma, Tania Tiepolo, Chiara Pellegrini, Patrizia Sabatelli, Alessia Angelin, Francesca Gualandi, Sergio Squarzoni, Paolo Bernardi, Nadir M. Maraldi, Luciano Merlini, Anna Urciuolo |
---|---|
Přispěvatelé: | Sabatelli P, Palma E, Angelin A, Squarzoni S, Urciuolo A, Pellegrini C, Tiepolo T, Bonaldo P, Gualandi F, Merlini L, Bernardi P, Maraldi NM. |
Jazyk: | angličtina |
Rok vydání: | 2011 |
Předmět: |
ULLRICH
Pathology Physiology Clinical Biochemistry Apoptosis Mitochondrion CONTRACTURES Muscular Dystrophies Collagen VI Cyclosporin a Original Research Articles Outcome Assessment Health Care Medicine Myocyte ULTRASTRUCTURAL DEFECTS Child Cells Cultured Clinical Trials as Topic Cultured COL6A1 GENE Bethlem myopathy BETHLEM MYOPATHY congenital muscolar dystrophy Skeletal Middle Aged Mitochondria medicine.anatomical_structure Phenotype Muscle medicine.symptom Adult medicine.medical_specialty Contracture Adolescent Ullrich congenital muscular dystrophy Cells Collagen Type VI Fibroblasts Humans Muscle Skeletal Muscular Diseases Outcome Assessment (Health Care) Patient Selection Primary Cell Culture Sclerosis Cell Biology MUSCLE APOPTOSIS Myopathy Fibroblast MUTATIONS business.industry medicine.disease DYSFUNCTION MITOCHONDRIAL PERMEABILITY TRANSITION Immunology business |
Zdroj: | Journal of Cellular Physiology |
ISSN: | 1097-4652 0021-9541 |
Popis: | Collagen VI myopathies (Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM), and myosclerosis myopathy) share a common pathogenesis, that is, 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 nine 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. J. Cell. Physiol. 227: 2927–2935, 2012. © 2011 Wiley Periodicals, Inc. |
Databáze: | OpenAIRE |
Externí odkaz: |