Article
Endocrinology & Metabolism
Fabiola Marino, Mariangela Scalise, Nadia Salerno, Luca Salerno, Claudia Molinaro, Donato Cappetta, Michele Torella, Marta Greco, Daniela Foti, Ferdinando C. Sasso, Pasquale Mastroroberto, Antonella De Angelis, Georgina M. Ellison-Hughes, Maurilio Sampaolesi, Marcello Rota, Francesco Rossi, Konrad Urbanek, Bernardo Nadal-Ginard, Daniele Torella, Eleonora Cianflone
Summary: Diabetes mellitus affects the biology of cardiac stem/progenitor cells, inhibiting their regenerative potential. By clearing senescent cells, the function of these cells can be restored, resulting in improved cardiac function in diabetic patients.
Article
Cell & Tissue Engineering
Robin Duelen, Domiziana Costamagna, Guillaume Gilbert, Liesbeth De Waele, Nathalie Goemans, Kaat Desloovere, Catherine M. Verfaillie, Karin R. Sipido, Gunnar M. Buyse, Maurilio Sampaolesi
Summary: This study utilized DMD patient-specific hiPSCs to model cardiomyopathy and uncovered the mechanism of oxidative stress in DMD cardiomyocytes. Targeting ROS production and preventing the detrimental effects of NOX4 on DMD CMs were proposed as promising therapeutic strategies.
Review
Cell Biology
Laura Yedigaryan, Martina Gatti, Vittoria Marini, Tullia Maraldi, Maurilio Sampaolesi
Summary: Cachexia and sarcopenia are significant conditions involving muscle loss, which can lead to mortality and disability. MicroRNAs play a key role in the development of muscle wasting in both cachexia and sarcopenia. Understanding the epigenetic mechanisms related to muscle loss in these conditions can help identify potential therapeutic interventions.
Article
Cell Biology
Vittoria Marini, Fabiola Marino, Flaminia Aliberti, Nefele Giarratana, Enrico Pozzo, Robin Duelen, Alvaro Cortes Calabuig, Rita La Rovere, Tim Vervliet, Daniele Torella, Geert Bultynck, Maurilio Sampaolesi, Yoke Chin Chai
Summary: In this study, cardiac organoids were generated from patient-derived induced pluripotent stem cells to model Duchenne Muscular Dystrophy (DMD)-related cardiomyopathy. The organoids exhibited progressive loss of sarcoglycan localization, endoplasmic reticulum stress, cardiomyocyte deterioration, fibrosis, and aberrant adipogenesis over time. RNA sequencing analysis identified distinct transcriptomic profiles and crucial miRNAs associated with DMD-related cardiomyopathy. These findings suggest the potential for developing in vitro 3D human cardiac-mimics to study DMD-related cardiomyopathies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Medicine, Research & Experimental
SungWoo Choi, Giulia Ferrari, Louise A. Moyle, Kirsty Mackinlay, Naira Naouar, Salma Jalal, Sara Benedetti, Christine Wells, Francesco Muntoni, Francesco Saverio Tedesco
Summary: Muscle satellite stem cells (MuSCs) play a crucial role in muscle growth and regeneration. Researchers have found that DLL4 and PDGF-BB can enhance the migration capacity of myogenic progenitors derived from human induced pluripotent stem cells (hiPSCs), bringing hiPSCs closer to potential applications in muscle gene and cell therapies.
EMBO MOLECULAR MEDICINE
(2022)
Article
Cell Biology
Domiziana Costamagna, Valerie Casters, Marc Beltra, Maurilio Sampaolesi, Anja Van Campenhout, Els Ortibus, Kaat Desloovere, Robin Duelen
Summary: This study generated in vitro human neuromuscular junctions (NMJs) using a microfluidic strategy from patient-specific induced pluripotent stem cell (hiPSC) lines to model disease-relevant neuropathologic processes in hereditary spastic paraplegia (HSP). The unique strength of this NMJ model is its ability to generate lower motor neurons (MNs) and myotubes from autologous hiPSC origin while maintaining the genetic background of HSP patient donors. The study found that HSP-derived lines exhibited axonal swellings, reduced levels of SPASTIN protein, and impaired NMJ profiles, offering unique tools to study the pathologic mechanisms of HSP.
Article
Multidisciplinary Sciences
Marc Beltra, Fabrizio Pin, Domiziana Costamagna, Robin Duelen, Alessandra Renzini, Riccardo Ballaro, Lorena Garcia-Castillo, Ambra Iannuzzi, Viviana Moresi, Dario Coletti, Maurilio Sampaolesi, Fabio Penna, Paola Costelli
Summary: This study reveals that overexpression of PGC-1 alpha in myofibers alters the proportion of MuSCs and ISCs, leading to enhanced fusion of myogenic progenitors with recipient myofibers and reduced adipogenesis in skeletal muscle.
Article
Cell Biology
Tim Vervliet, Robin Duelen, Ankit Pradhan, Rita La Rovere, H. Llewelyn Roderick, Maurilio Sampaolesi
Summary: Bcl-2 plays a crucial role in the differentiation of cardiomyocytes, and its loss delays the induction of pluripotent stem cells into cardiomyocytes, leading to reduced expression and activity of the cardiomyocyte Ca2+ toolkit, as well as decreased c-Myc expression and nuclear localization in the early phase of cardiac differentiation.
JOURNAL OF CELL SCIENCE
(2023)
Review
Genetics & Heredity
Giulio Cossu, Rossana Tonlorenzi, Silvia Brunelli, Maurilio Sampaolesi, Graziella Messina, Emanuele Azzoni, Sara Benedetti, Stefano Biressi, Chiara Bonfanti, Laricia Bragg, Jordi Camps, Ornella Cappellari, Marco Cassano, Fabio Ciceri, Marcello Coletta, Diego Covarello, Stefania Crippa, M. Gabriella Cusella-De Angelis, Luciana De Angelis, Arianna Dellavalle, Jordi Diaz-Manera, Daniela Galli, Francesco Galli, Cesare Gargioli, Mattia F. M. Gerli, Giorgia Giacomazzi, Beatriz G. Galvez, Hidetoshi Hoshiya, Maria Guttinger, Anna Innocenzi, M. Giulia Minasi, Laura Perani, Stefano C. Previtali, Mattia Quattrocelli, Martina Ragazzi, Urmas Roostalu, Giuliana Rossi, Raffaella Scardigli, Dario Sirabella, Francesco Saverio Tedesco, Yvan Torrente, Gonzalo Ugarte
Summary: In 2002, we discovered a group of vessel-associated progenitors called mesoangioblasts (MABs). Studies over the past decade have shown that muscle development and regeneration are more complex than previously thought. We identified the origin of MABs as partly from the embryonic aorta and later from the microvasculature of skeletal muscle. MABs could be expanded in vitro and cross the vessel wall, making them a potential choice for cell therapy of muscular dystrophies.
FRONTIERS IN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Martina Gatti, Katarina Stoklund Dittlau, Francesca Beretti, Laura Yedigaryan, Manuela Zavatti, Pietro Cortelli, Carla Palumbo, Emma Bertucci, Ludo van den Bosch, Maurilio Sampaolesi, Tullia Maraldi
Summary: Neuromuscular junctions are important for communication between spinal motor neurons and skeletal muscle, and their vulnerability in degenerative diseases like muscle atrophy is poorly understood. Recent studies have shown the regenerative potential of stem cells and extracellular vesicles in muscle fiber regeneration, but their role in counteracting NMJ perturbations is not clear. In this study, a co-culture system was used to investigate the effects of AFSC-derived EVs on NMJ alterations induced by muscle atrophy. The presence of EVs reduced morphological and functional defects and prevented oxidative stress in atrophic myotubes. This study provides a valuable tool for studying MN and myotube interactions and demonstrates the efficacy of AFSC-EVs in counteracting NMJ perturbations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Luca Pinton, Moustafa Khedr, Valentina M. Lionello, Shilpita Sarcar, Sara M. Maffioletti, Sumitava Dastidar, Elisa Negroni, SungWoo Choi, Noreen Khokhar, Anne Bigot, John R. Counsell, Andreia Sofia Bernardo, Peter S. Zammit, Francesco Saverio Tedesco
Summary: This article presents a protocol for the modular 3D bioengineering of multilineage skeletal muscles from human induced pluripotent stem cells, and provides assays to characterize morphological and functional features of the artificial muscle constructs. These bioengineered muscles have the ability to recapitulate morphological and functional features of human skeletal muscle, making them a powerful tool for studying muscle pathology and developing neuromuscular and musculoskeletal therapies.
Review
Physiology
Laura Yedigaryan, Maurilio Sampaolesi
Summary: Duchenne muscular dystrophy (DMD) is a severe disorder caused by mutations in the dystrophin gene, leading to muscle fiber degradation and weakness. Extracellular vesicles (EVs), secreted by cells, may play a role in DMD pathology and could serve as biomarkers for specific pathological processes. Additionally, EVs can be used for targeted cargo delivery and inhibition of EV secretion, providing potential therapeutic strategies for DMD.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Cell Biology
M. Corvelyn, J. Meirlevede, J. Deschrevel, E. Huyghe, E. De Wachter, G. Gayan-Ramirez, M. Sampaolesi, A. Van Campenhout, K. Desloovere, D. Costamagna
Summary: Cerebral palsy (CP) is a common condition causing lifelong physical disability in children. Previous studies have shown changes in muscle properties, such as decreased number of satellite cells and altered fusion capacity. However, these observations vary widely among studies, possibly due to differences in patient population, lack of control data, methodology, and muscle assessment. This study aimed to further investigate CP muscle pathology and confirm previous findings of increased satellite cell fusion capacity.
Review
Biotechnology & Applied Microbiology
Dries De Wolf, Kshitiz Singh, Marinee K. Chuah, Thierry Vandendriessche
Summary: Extensive preclinical research has led to the recent regulatory approval of gene therapy products for hemophilia. Roctavian and Hemgenix have shown significant efficacy and safety in clinical trials, resulting in increased levels of clotting factors and reduced bleeding episodes for patients. However, there is variability in patient response and short-term liver inflammation was observed. Longer follow-up studies are needed to determine if lifelong expression of clotting factors can be achieved. Next-generation gene editing technologies offer new prospects for a sustained cure for hemophilia.
HUMAN GENE THERAPY
(2023)
Article
Cell Biology
Domiziana Costamagna, Valeria Bastianini, Marlies Corvelyn, Robin Duelen, Jorieke Deschrevel, Nathalie De Beukelaer, Hannah De Houwer, Maurilio Sampaolesi, Ghislaine Gayan-Ramirez, Anja Van Campenhout, Kaat Desloovere
Summary: This study aims to clarify the impact of BoNT on growing muscles by analyzing the effect of BoNT on muscle stem cells in vitro, and by following the effect of in vivo BoNT administration on these cells obtained from children with CP. The results show that in vitro BoNT does not affect muscle differentiation or collagen production, but it does affect neuromuscular junctions. Further studies are needed to understand the long-term and collateral effects of BoNT in the muscles of children with CP.
