1,721,072 research outputs found
Gene therapy of skin adhesion disorders (mini review)
No full textGene therapy is a potential treatment for severe inherited disorders for which there is little hope of finding a conventional cure. These include lethal diseases like immunodeficiencies and metabolic disorders, and non lethal conditions associated to poor quality of life and life-long symptomatic treatments, like muscular dystrophy, cystic fibrosis or thalassemia. Skin adhesion defects belong to both groups. For the non-lethal forms, gene therapy, or transplantation of cultured skin derived from genetically corrected epidermal stem cells, represents a very attractive therapeutic option, and potentially a definitive treatment. Recent advances in gene transfer and stem cell culture technology are making this option closer than ever. This paper critically reviews the progress and prospects of gene therapy for skin adhesion defects, and the factors currently limiting its development
Myogenic stem cells from the bone marrow: a therapeutic alternative for muscular dystrophy?
No full textDifferentiated muscle fibres can be formed by transplanted haematopoietic stem cells in models of acute or chronic muscle regeneration, including the dystrophin-deficient mdx mouse. Muscle-forming activity can be found in adult, foetal and embryonic haematopoietic tissues. The blood-to-muscle transition may be due to transdifferentiation of haematopoietic progenitors in response to local signals provided by the regenerating muscle. These signals are only poorly provided by the muscle of the mdx mouse, since transplantation into these mice of normal C57Bl/6 bone mar-row gives rise only to a minimal number of muscle fibres expressing the normal dystrophin protein (<1%) throughout the animal life span. Expansion and active recruitment to myogenic differentiation of transplanted haematopoietic cells are therefore critical factors for a future use of bone marrow transplantation in cell/gene therapy of muscular dystrophy. (C) 2002 Elsevier Science B.V. All rights reserved
Site-specific integration by the adeno-associated virus rep protein
No full textInserting genetic information at precise locations into the human genome has been the goal of gene transfertechnology for almost two decades. The spectacular progress of mammalian genetics in the last two decades has led to thedevelopment of technology for genome editing and homologous recombination in human somatic cells that is finally approachingefficiency compatible with clinical application. Site-specific integration, or the insertion of genes at known locationsby enzymes with target recognition capacity, has progressed slowly but steadily in recent years, and could verywell be the basis of the next generation of gene transfer technology. This review focuses on the use of Rep, the replicase/integrase of the adeno-associated virus (AAV), to insert genes at the natural AAV integration site on human chromosome19. This region (AAVS1) has characteristics that make it an ideal target for somatic transgenesi
Myogenic stem cells for the therapy of primary myopathies: wishful thinking or therapeutic perspective?
No full textPrimary myopathies are characterized by a progressive wasting of skeletal muscle that leads to deterioration of movements and, in the most severe cases, such as in Duchenne’s muscular dystrophy (DMD), to complete paralysis and death. Most myopathies in which the molecular defect has been identified are due to mutations affecting proteins that form a supramolecular link between the cytoskeleton and the extracellular matrix, such as dystrophin, the mutated protein in DMD. In the absence of one of these proteins, mechanical stress associated with contraction progressively leads to degeneration of the muscle fiber, although the underlying mechanisms are still poorly understood. In the first phase of the disease, new muscle fibers are formed by fusion of resident myoblasts, called satellite cells, which also bear the molecular defect of the fibers that they replace, and hence undergo the same fate. Once the proliferation potential of satellite cells is exhausted, there is no further regeneration and the skeletal muscle is replaced by connective tissu
Site-specific integration into the human genome: Ready for clinical application?
No full textInserting genetic information at precise locations into the human genome has been the goal of the gene therapy community for almost two decades. Despite their spectacular progress in many fields of mammalian genetics, genome editing and homologous recombination are still too inefficient to be applied to human primary cells and tissues, the targets of any medical application. Site-specific integration, or the insertion of genes at known locations by enzymes that target recognition capacity, has progressed slowly but steadily in recent years, and could very well be the basis of the next generation of gene transfer technology
Medicina rigenerativa e nuove frontiere terapeutiche
No full textLo sviluppo delle colture cellulari ha messo in evidenza che le cellule adulte (non più allo stadio embrionale) potevano essere manipolate e dare origine non solo alla proliferazione, che ne aumentava il numero, ma anche al differenziamento che garantiva
che quelle cellule potessero svolgere le funzioni più "specializzate" dei tessuti. Tutto ciò ha aperto prospettive completamente nuove alla medicina e si è fatta strada l'idea di costruire "pezzi di ricambio" o, comunque, imparare a trasmettere informazioni ad un tessuto danneggiato perché questo venisse riparato.
La pionieristica chirurgia del cardiochirurgo C. Barnard ha dimostrato che il cuore di un individuo poteva essere trapiantato in un altro individuo; oggi questo concetto si sta sostituendo con l'idea che si può tentare di ricostruire un tessuto di un paziente in laboratorio, partendo dalle sue stesse cellule. L'uso di cellule "autologhe" (cioè dello stesso individuo e non di un donatore) per ricostruire o modificare le funzioni di un tessuto, evita tutti i problemi di rigetto e la tossicità dei farmaci che, normalmente, si somministrano per ridurre le reazioni di rigetto.
La lista di tessuti che, potenzialmente, possono essere ricostruiti (o ingegnerizzati) è in crescita. Tutto ciò è dovuto in larga parte ai recenti progressi nello studio delle cellule staminali e alla individuazione delle caratteristiche biologiche uniche di queste cellule, sebbene non tutte le terapie basate sulle cellule staminali prevedano la ricostruzione del tessuto in vitro, come ad esempio alcune terapie che utilizzano le cellule staminali neuronali, ma
piuttosto la stimolazione di cellule endogene. Altre terapie, inoltre, prevedono l'uso di cellule staminali geneticamente modificate per produrre sostanze con funzioni terapeutiche.
Bisogna ricordare che, nonostante le aspettative, il passaggio alla applicazione clinica è stato raggiunto, ad oggi, solo in poche aree, in particolare in quelle nelle quali si era sviluppata una conoscenza più approfondita della biologia delle cellule staminali di quel distretto corporeo. I tessuti che oggi sono ricostruiti ed applicati con relativa facilità comprendono una ampia gamma di superfici epiteliali (pelle, cornea, congiuntiva e membrane mucose),
tessuti scheletrici e sistema ematopoietico. Tra questi, quelli che sono stati geneticamente modificati ed utilizzati con successo per applicazione clinica, includono il sistema ematopoietico e gli epiteli. Questi sistemi sono intrinsecamente differenti nella loro capacità
di autorinnovarsi, nella loro fisiologia e nella struttura fisica. La valutazione e lo studio delle diversità intrinseche ad ogni organo o sistema e la conoscenza della regolazione delle sue cellule staminali è essenziale per lo sviluppo di adeguate strategie di intervento clinico nei vari distretti corporei e nelle diverse patologie.
Il capitolo descrive alcuni tra i diversi modelli possibili e alcune problematiche legate all'uso delle due branche principali della medicina rigenerativa: la terapia cellulare e la terapia genica
Functional dissection of a transcriptionally active, target specific Hox/Pbx complex.
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Gene therapy of inherited skin adhesion disorders: a critical overview
No full textGene therapy has the potential to treat devastating inherited diseases for which there is little hope of finding a conventional cure. These include lethal diseases, like immunodeficiencies or several metabolic disorders, or conditions associated with a relatively long life expectancy but poor quality of life and expensive and life-long symptomatic treatments, such as muscular dystrophy, cystic fibrosis and thalassaemia. Skin adhesion defects belong to both groups. For the nonlethal forms, gene therapy, or transplantation of cultured skin derived from genetically corrected epidermal stem cells, represents a very attractive therapeutic option, and potentially a definitive treatment. Recent advances in gene transfer and stem cell culture technology are making this option closer than ever. This paper critically reviews the progress and prospects of gene therapy for epidermolysis bullosa, and the technical and nontechnical factors currently limiting its development
Genetic modification of somatic stem cells. The progress, problems and prospects of a new therapeutic technology
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