Noninvasive imaging procedures will be important for stem cell therapy for muscular dystrophy (MD). Mesoangioblasts regenerate muscle in animal models of muscular dystrophy. In this study, superparamagnetic iron oxide nanoparticles were used to visualize mesoangioblasts in vivo with MRI. Mesoangioblasts incorporated superparamagnetic iron oxide without transfection reagents, and cell differentiation was not negatively impacted. A custom-built radiofrequency coil with an adjustable field of view and 14.1 T magnet were used for whole-body MRI of mice. High-resolution images of mesoangioblasts in skeletal and cardiac muscle of Mdx mice were obtained following local delivery. Labeled cells were verified by Prussian blue staining and dystrophin expression, indicating that the wild-type mesoangioblasts survived and differentiated in muscle. Iron-labeled cells were detected with MRI in vivo 6 months following intracardiac injection but were determined to be activated macrophages. Iron-labeled cells were not detected by MRI following systemic delivery but were present in skeletal and cardiac muscle, visualized by Prussian blue staining. Systemically delivered mesoangioblasts were detected in lungs by Prussian blue staining and DiI but not by MRI in our study. MRI may be useful for short-term tracking of mesoangioblasts delivered locally but not for long-term monitoring or detection after systemic delivery.
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http://dx.doi.org/10.1002/mrm.22942 | DOI Listing |
Cell Rep Med
December 2024
Laboratory of Precision Nanomedicine, The Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel-Aviv, Israel; Department of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel; Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv, Israel; Cancer Biology Research Center, Tel Aviv University, Tel Aviv, Israel. Electronic address:
Muscular dystrophies are a group of heterogenic disorders characterized by progressive muscle weakness, the most common of them being Duchenne muscular dystrophy (DMD). Muscular dystrophies are caused by mutations in over 50 distinct genes, and many of them are caused by different genetic mechanisms. Currently, none of these diseases have a cure.
View Article and Find Full Text PDFStem Cell Res
December 2024
Department of Cell and Developmental Biology, University College London, London WC1E 6DE, UK; Stem Cells and Neuromuscular Regeneration Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital for Children, London, UK. Electronic address:
Ullrich congenital muscular dystrophy (UCMD) represents the most severe subtype of collagen VI-related dystrophies (COL6-RDs), a spectrum of rare extracellular matrix disorders affecting skeletal muscle and connective tissue. Here, we generated an induced pluripotent stem cell (iPSC) line (CRICKi021-A) from a UCMD patient with de novo dominant-negative mutation in COL6A1 gene by reprogramming dermal fibroblasts using a non-integrating mRNA-based protocol. The resulting human iPSCs displayed normal morphology, expressed pluripotency-associated markers and differentiated into the three germ layers.
View Article and Find Full Text PDFUnlabelled: RNA-driven protein aggregation leads to cellular dysregulation by sequestering regulatory proteins, disrupting normal cellular processes, and contributing to the development of diseases and tumorigenesis. Here, we show that double homeobox 4 (DUX4), an early embryonic transcription factor and causative gene of facioscapulohumeral muscular dystrophy (FSHD), induces the accumulation of stable intranuclear RNAs, including nucleolar-associated RNA and human satellite II (HSATII) repeat RNA. Stable intranuclear RNAs drive protein aggregation in DUX4-expressing muscle cells.
View Article and Find Full Text PDFAlthough current treatments for Duchenne Muscular Dystrophy (DMD) have proven to be effective in delaying myopathy, there remains a strong need to identify novel targets to develop additional therapies. Mitochondrial dysfunction is an early pathological feature of DMD. A fine balance of mitochondrial dynamics (fission and fusion) is crucial to maintain mitochondrial function and skeletal muscle health.
View Article and Find Full Text PDFEMBO J
January 2025
Telethon Institute of Genetics and Medicine (TIGEM), 80078, Pozzuoli, Italy.
Endoplasmic reticulum (ER) plasticity and ER-phagy are intertwined processes essential for maintaining ER dynamics. We investigated the interplay between two isoforms of the ER-phagy receptor FAM134B in regulating ER remodeling in differentiating myoblasts. During myogenesis, the canonical FAM134B1 is degraded, while its isoform FAM134B2 is transcriptionally upregulated.
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