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
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