A5035597305- Muscle Physiology and Disorders
- CRISPR and Genetic Engineering
- Mesenchymal stem cell research
- Virus-based gene therapy research
- Tissue Engineering and Regenerative Medicine
- RNA Interference and Gene Delivery
- Organ and Tissue Transplantation Research
- Pluripotent Stem Cells Research
- Neurogenetic and Muscular Disorders Research
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Photoreceptor and optogenetics research
- Viral Infections and Immunology Research
- Lipid Membrane Structure and Behavior
- Neurobiology and Insect Physiology Research
- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Transplantation: Methods and Outcomes
- Neuroscience and Neural Engineering
- Xenotransplantation and immune response
- Exercise and Physiological Responses
- CAR-T cell therapy research
- Prosthetics and Rehabilitation Robotics
- Cytomegalovirus and herpesvirus research
Université Laval
2016-2025
Centre hospitalier de l'Université Laval
2015-2024
Stem Cell Network
2024
Centre hospitalier universitaire de Québec
2011-2023
Wilfrid Laurier University
2002-2022
Polytechnique Montréal
2019-2021
Emory University
2011
Muscular Dystrophy Association
1999-2005
Association Francaise contre les Myopathies
2005
In-Q-Tel
2003
The effects of myoblast transplantations without an immunosuppressive treatment on muscle strength, and the formation dystrophin-positive fibers was studied in five young boys with Duchenne muscular dystrophy (DMD) using a triple blind design. Injections myoblasts were made into one biceps brachii (BB), opposite BB, used as control, sham-injected; experimenters patient to myoblast-injected side. At same time, also injected left tibialis anterior (TA) these patients. strength developed during...
Duchenne muscular dystrophy is a lethal recessive disease characterized by widespread muscle damage throughout the body. This increases difficulty of cell or gene therapy based on direct injections into muscles. One way to circumvent this obstacle would be use circulating cells capable homing sites lesions. Here, we showed that stem antigen 1 (Sca-1), CD34 double-positive purified from tissues newborn mice are multipotent in vitro and can undergo both myogenic multimyeloid differentiation....
Myoblasts from immunocompatible donors have been transplanted into the muscles (tibialis anterior, biceps brachii, and/or extensor carpi radialis longus) of 4 Duchenne patients in advanced stages disease. Although no immunosuppressive treatment was used, none showed any clinical signs rejection such as fever, redness, and inflammation. One patient transiently produced antibodies against donor myoblasts determined by cytofluorometric analysis. This 2 others were shown to form their donor's...
A clinical trial was conducted to test a new protocol of normal muscle precursor cell (MPC) allotransplantation in skeletal muscles patients with Duchenne muscular dystrophy (DMD). Cultured MPCs obtained from one the patient's parents were implanted 0.25 or 1 cm3 Tibialis anterior 9 DMD. MPC injections placed 2 mm each other, and similar pattern saline done contralateral muscle. The immunosuppressed tacrolimus. Muscle biopsies performed at injected sites 4 weeks later. In cell-grafted sites,...
Abstract Transgenic CD1 mice expressing β‐galactosidase were used as myoblast donors. The myoblasts injected in normal or mdx muscles previously irradiated and with notexin. Twenty‐eight days after transplantation, the percentage of muscle fibers β‐galactosidase‐positive was low not immunosuppressed but high (80%) those treated FK506. In mice, also dystrophin positive. Most FK506 produced antibodies against donor myoblasts. These results indicate that is a very useful immunosuppressive drug...
Three Duchenne muscular dystrophy (DMD) patients received injections of myogenic cells obtained from skeletal muscle biopsies normal donors. The (30 x 10 (6)) were injected in 1 cm3 the tibialis anterior by 25 parallel injections. We performed similar patterns saline contralateral muscles as controls. tacrolimus for immunosuppression. Muscle at sites 4 weeks later. observed dystrophin-positive myofibers cell-grafted amounting to 9 (patient 1), 6.8 2), and 11% 3). Since 2 had identified...
Genome editing with engineered nucleases has recently emerged as an approach to correct genetic mutations by enhancing homologous recombination a DNA repair template. However, many diseases, such Duchenne muscular dystrophy (DMD), can be treated simply correcting disrupted reading frame. We show that genome transcription activator-like effector (TALENs), without template, efficiently the frame and restore expression of functional dystrophin protein is mutated in DMD. TALENs were mediate...
Human embryonic stem cells (hESCs) and human-induced pluripotent (hiPSCs) have an endless self-renewal capacity can theoretically differentiate into all types of lineages. They thus represent unlimited source for therapies regenerative diseases, such as Duchenne muscular dystrophy (DMD), tissue repair in specific medical fields. However, at the moment, low number efficient lineage differentiation protocols compromises their use medicine. We developed a two-step procedure to hESCs dystrophic...
Despite good initial success in vivo, gene transfer using first-generation replication-defective adenovirus has been reported to lead transient reporter expression and trigger inflammatory reactions various organs animal models. To gain more knowledge on this phenomenon, immune were investigated following vivo transfection of adult immunocompetent mouse muscle a ΔE1/E3a adenoviral vector encoding β-galactosidase (β-Gal) cassette. Cellular humoral reactions, rejection β-Gal-positive fibers,...
SCID mouse tibialis anterior muscles were first irradiated to prevent regeneration by host myoblasts and injected with notexin damage the muscle fibers trigger regeneration. The then roughly 5 million human myoblasts. 1 mo later, 16-33% of normal number present in muscle, because incomplete However, > 90% these contained dystrophin. Some newly formed had an accumulation dystrophin desmin on a part their membrane. Such accumulations have been demonstrated at neuromuscular junctions before...
Myoblast transplantation is a potential treatment for Duchenne muscular dystrophy. One of the problems possibly responsible limited success clinical trials rapid death myoblasts after transplantation. To investigate this problem, expressing beta-galactosidase were injected in tibialis anterior muscles mice. Beta-galactosidase activity was reduced by 74.7% 3 days. observed at days to 57.2% when hosts irradiated. This result suggested that host cells contributing phenomenon. Transplantation...
Duchenne muscular dystrophy (DMD) is characterized by the absence of dystrophin. We tested ability lentiviral vectors to deliver a transgene into myogenic cells before their transplantation. Enhanced green fluorescent protein (eGFP) was efficiently transferred and eGFP-positive fibers were generated following An eGFP-micro-dystrophin under control cytomegalovirus promoter then with same viral vector but caused some toxicity mono-nucleated cells. used instead muscle creatine kinase promoter....
The CRISPR/Cas9 system is a great revolution in biology. This technology allows the modification of genes vitro and vivo wide variety living organisms. In most Duchenne muscular dystrophy (DMD) patients, expression dystrophin (DYS) protein disrupted because exon deletions result frame shift. We present here CRISPR-induced deletion (CinDel), new promising genome-editing to correct DMD gene. strategy based on use two gRNAs targeting specifically exons that precede follow patient pair induced...
Duchenne muscular dystrophy (DMD), a severe hereditary disease affecting 1 in 3,500 boys, mainly results from the deletion of exon(s), leading to reading frameshift DMD gene that abrogates dystrophin protein synthesis. Pairs sgRNAs for Cas9 Staphylococcus aureus were meticulously chosen restore normal frame and also produce with normally phased spectrin-like repeats (SLRs), which is not usually obtained by skipping or complete exons. This can, however, be rare instances where exon intron...
Extracellular vesicles (EVs) mediate intercellular biomolecule exchanges in the body, making them promising delivery vehicles for therapeutic cargo. Genetic engineering by CRISPR system is an interesting avenue genetic diseases such as Duchenne muscular dystrophy (DMD). We developed a simple method loading EVs with ribonucleoproteins (RNPs) consisting of SpCas9 proteins and guide RNAs (gRNAs). were first purified from human or mouse serum using ultrafiltration size-exclusion chromatography....