Generation of two genomic-integration-free DMD iPSC lines with mutations affecting all dystrophin isoforms and potentially amenable to exon-skipping

Publication date: Available online 1 February 2020Source: Stem Cell ResearchAuthor(s): Giulia Ferrari, Francesco Muntoni, Francesco Saverio TedescoAbstractDuchenne muscular dystrophy (DMD) is the most common paediatric muscular dystrophy and is caused by mutations in the DYSTROPHIN gene. We generated two induced pluripotent stem cell (iPSC) lines from DMD patients with nonsense mutations in exons 68 (UCLi011-A) or 70 (UCLi012-A) by transfecting reprogramming mRNAs. Both mutations affect expression of all dystrophin isoforms. iPSCs expressed pluripotency-associated markers, differentiated into cells of the three germ layers in vitro and had normal karyotypes. The selected mutations are potentially amenable to read-through therapies, exon-skipping and gene-editing. These new iPSCs are also relevant to study DYSTROPHIN role in tissues other than skeletal muscle.
Source: Stem Cell Research - Category: Stem Cells Source Type: research

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Tupler Facioscapulohumeral muscular dystrophy (FSHD) has been associated with the genetic and epigenetic molecular features of the CpG-rich D4Z4 repeat tandem array at 4q35. Reduced DNA methylation of D4Z4 repeats is considered part of the FSHD mechanism and has been proposed as a reliable marker in the FSHD diagnostic procedure. We considered the assessment of D4Z4 DNA methylation status conducted on distinct cohorts using different methodologies. On the basis of the reported results we conclude that the percentage of DNA methylation detected at D4Z4 does not correlate with the disease status. Overall, data suggest th...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Review Source Type: research
Publication date: Available online 31 January 2020Source: Stem Cell ResearchAuthor(s): Kseniya Perepelina, Polina Klauzen, Aleksandr Khudiakov, Anna Zlotina, Yulia Fomicheva, Dmitry Rudenko, Mikhail Gordeev, Alexey Sergushichev, Anna Malashicheva, Anna KostarevaAbstractMutations in LMNA gene are known to cause a broad range of diseases called laminopathies. We have generated two induced pluripotent stem cell lines FAMRCi006-A and FAMRCi006-B from a patient carrying LMNA p. p.Arg527Pro mutation associated with Emery–Dreifuss muscular dystrophy and dilated cardiomyopathy. Patient-specific peripheral blood mononuclear c...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
Abstract The gene therapy approach aiming at curing various human diseases began to develop as a technology from early eighties of the last century. To date the delivery of therapeutic genes are mainly mediated by virus-based, predominantly, non-integrated virus vectors. These gene delivery approaches have several fundamental limitations on the way of efficient deployment in clinical gene therapy. A totally different approach was suggested about 20 years ago when episomal non-integrative artificial chromosome-based vectors featuring large size inserts (even native gene loci) advanced to the stage. Since then numer...
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research
UCLA researchers are part of an international team that reported the use of a stem cell gene therapy to treat nine people with the rare, inherited blood disease known as X-linked chronic granulomatous disease, or X-CGD. Six of those patients are now in remission and have stopped other treatments. Before now, people with X-CGD – which causes recurrent infections, prolonged hospitalizations for treatment, and a shortened lifespan – had to rely on bone marrow donations for a chance at remission.“With this gene therapy, you can use a patient’s own stem cells instead of donor cells for a transplant,&rdqu...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
AbstractPurpose of ReviewThis paper reviews the enhanced therapeutic effects of rehabilitation and regenerative medicine toward Duchenne muscular dystrophy.Recent FindingsDuchenne muscular dystrophy (DMD) is one of the most severe forms of muscle disorders. Muscle in DMD patients is extremely fragile and can be damaged even during normal daily activity. There is little in the way of treatment for the disease and no cure. Some investigators have been developing cell therapies for DMD by generating muscle stem cells from human-induced pluripotent stem (iPS) cells and other progenitor/stem cells. Although reports have shown d...
Source: Current Physical Medicine and Rehabilitation Reports - Category: Rehabilitation Source Type: research
In conclusion, this study demonstrates that dystrophic skeletal muscles express and secrete significant levels of FGF‐21, which negatively regulates bone homeostasis and represents an important patho logical factor for the development of bone abnormalities in DMD. The current study highlights the importance of muscle/bone cross talk via muscle derived factors (myokines) in the pathogenesis of bone abnormalities in DMD.This article is protected by copyright. All rights reserved.
Source: Journal of Bone and Mineral Research - Category: Orthopaedics Authors: Tags: Original Article Source Type: research
This study demonstrates for the first time that senescent cells secrete functional LTs, significantly contributing to the LTs pool known to cause or exacerbate idiopathic pulmonary fibrosis. Against Senolytics https://www.fightaging.org/archives/2019/11/against-senolytics/ There is no consensus in science that is so strong as to have no heretics. So here we have an interview with a naysayer on the matter of senolytic treatments, who argues that the loss of senescent cells in aged tissues will cause more harm to long-term health than the damage they will do by remaining. To be clear, I think this to be a ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Publication date: Available online 23 November 2019Source: Stem Cell ResearchAuthor(s): Jingyun Guan, Xinnong Liu, Haiyan Zhang, Xiaomeng Yang, Yanyan Ma, Yue Li, Zhongtao Gai, Yi LiuAbstractDuchenne muscular dystrophy (DMD), an X-linked genetic disorder characterized by progressive muscle weakness and atrophies affecting skeletal and cardiac muscles, is caused by mutations in dystrophin (DMD) gene that spans 79 exons. Here, we generated iPSCs from a Chinese patient with 49 to 50 exons deletion in DMD gene by reprogramming peripheral blood mononuclear cells with non-integrating vectors. The generated iPSCs line (SDQLCHi007...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
Dogs are an interesting species when it comes to the study of aging. Firstly they are much closer to human metabolism and cellular biochemistry than mice, and secondly selective breeding has generated lineages with a very wide range of sizes and life spans. Thirdly, they occupy a good compromise position in the range of life spans, study cost, and similarity to humans. Mice live short lives, so studies are rapid and comparatively cheap, but there are sizable, important differences between mouse and human biochemistry. Humans live so long that most studies of aging are simply out of the question. Even in non-human primates ...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
Publication date: Available online 25 October 2019Source: Stem Cell ResearchAuthor(s): Lionel O. Mavoungou, Samuel Neuenschwander, Uyen Pham, Pavithra S. Iyer, Nicolas MermodABSTRACTDuchenne muscular dystrophy (DMD) is a lethal muscle-wasting disease caused by the lack of dystrophin in muscle fibers that is currently without curative treatment. Mesoangioblasts (MABs) are multipotent progenitor cells that can differentiate to a myogenic lineage and that can be used to express Dystrophin upon transplantation into muscles, in autologous gene therapy approaches. However, their fate in the muscle environment remains poorly...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
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