Extracellular vesicle-derived miRNAs improve stem cell-based therapeutic approaches in muscle wasting conditions
Skeletal muscle holds an intrinsic capability of growth and regeneration both in physiological conditions and in case of injury. Chronic muscle illnesses, generally caused by genetic and acquired factors, lead to deconditioning of the skeletal muscle structure and function, and are associated with a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.977617/full |
| _version_ | 1828098752366247936 |
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| author | Laura Yedigaryan Ester Martínez-Sarrà Giorgia Giacomazzi Nefele Giarratana Bernard K. van der Veer Alessio Rotini Silvia Querceto Hanne Grosemans Álvaro Cortés-Calabuig Sara Salucci Michela Battistelli Elisabetta Falcieri Rik Gijsbers Mattia Quattrocelli Mattia Quattrocelli Kian Peng Koh Liesbeth De Waele Gunnar M. Buyse Rita Derua Maurilio Sampaolesi Maurilio Sampaolesi |
| author_facet | Laura Yedigaryan Ester Martínez-Sarrà Giorgia Giacomazzi Nefele Giarratana Bernard K. van der Veer Alessio Rotini Silvia Querceto Hanne Grosemans Álvaro Cortés-Calabuig Sara Salucci Michela Battistelli Elisabetta Falcieri Rik Gijsbers Mattia Quattrocelli Mattia Quattrocelli Kian Peng Koh Liesbeth De Waele Gunnar M. Buyse Rita Derua Maurilio Sampaolesi Maurilio Sampaolesi |
| author_sort | Laura Yedigaryan |
| collection | DOAJ |
| description | Skeletal muscle holds an intrinsic capability of growth and regeneration both in physiological conditions and in case of injury. Chronic muscle illnesses, generally caused by genetic and acquired factors, lead to deconditioning of the skeletal muscle structure and function, and are associated with a significant loss in muscle mass. At the same time, progressive muscle wasting is a hallmark of aging. Given the paracrine properties of myogenic stem cells, extracellular vesicle-derived signals have been studied for their potential implication in both the pathogenesis of degenerative neuromuscular diseases and as a possible therapeutic target. In this study, we screened the content of extracellular vesicles from animal models of muscle hypertrophy and muscle wasting associated with chronic disease and aging. Analysis of the transcriptome, protein cargo, and microRNAs (miRNAs) allowed us to identify a hypertrophic miRNA signature amenable for targeting muscle wasting, consisting of miR-1 and miR-208a. We tested this signature among others in vitro on mesoangioblasts (MABs), vessel-associated adult stem cells, and we observed an increase in the efficiency of myogenic differentiation. Furthermore, injections of miRNA-treated MABs in aged mice resulted in an improvement in skeletal muscle features, such as muscle weight, strength, cross-sectional area, and fibrosis compared to controls. Overall, we provide evidence that the extracellular vesicle-derived miRNA signature we identified enhances the myogenic potential of myogenic stem cells. |
| first_indexed | 2024-04-11T08:06:57Z |
| format | Article |
| id | doaj.art-75771e6b6f9f4141abd91f02144e00b8 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T08:06:57Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-75771e6b6f9f4141abd91f02144e00b82022-12-22T04:35:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.977617977617Extracellular vesicle-derived miRNAs improve stem cell-based therapeutic approaches in muscle wasting conditionsLaura Yedigaryan0Ester Martínez-Sarrà1Giorgia Giacomazzi2Nefele Giarratana3Bernard K. van der Veer4Alessio Rotini5Silvia Querceto6Hanne Grosemans7Álvaro Cortés-Calabuig8Sara Salucci9Michela Battistelli10Elisabetta Falcieri11Rik Gijsbers12Mattia Quattrocelli13Mattia Quattrocelli14Kian Peng Koh15Liesbeth De Waele16Gunnar M. Buyse17Rita Derua18Maurilio Sampaolesi19Maurilio Sampaolesi20Translational Cardiomyology Laboratory, Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven, Leuven, BelgiumTranslational Cardiomyology Laboratory, Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven, Leuven, BelgiumTranslational Cardiomyology Laboratory, Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven, Leuven, BelgiumTranslational Cardiomyology Laboratory, Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven, Leuven, BelgiumDepartment of Development and Regeneration, Laboratory for Stem Cell and Developmental Epigenetics, Stem Cell Institute, KU Leuven, Leuven, BelgiumTranslational Cardiomyology Laboratory, Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven, Leuven, BelgiumTranslational Cardiomyology Laboratory, Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven, Leuven, BelgiumTranslational Cardiomyology Laboratory, Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven, Leuven, BelgiumLaboratory for Cytogenetics and Genome Research, Department of Human Genetics, KU Leuven, Leuven, BelgiumCellular Signalling Laboratory, Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, ItalyDepartment of Biomolecular Sciences, Urbino University Carlo Bo, Urbino, ItalyDepartment of Biomolecular Sciences, Urbino University Carlo Bo, Urbino, ItalyLaboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, Leuven Viral Vector Core, KU Leuven, Leuven, BelgiumTranslational Cardiomyology Laboratory, Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven, Leuven, BelgiumCincinnati Children’s Hospital Medical Center, Department of Pediatrics, Heart Institute, University of Cincinnati College of Medicine and Molecular Cardiovascular Biology Division, Cincinnati, OH, United StatesDepartment of Development and Regeneration, Laboratory for Stem Cell and Developmental Epigenetics, Stem Cell Institute, KU Leuven, Leuven, BelgiumDepartment of Development and Regeneration, Pediatric Neurology, University Hospitals Leuven, KU Leuven, Leuven, BelgiumDepartment of Development and Regeneration, Pediatric Neurology, University Hospitals Leuven, KU Leuven, Leuven, BelgiumLaboratory of Protein Phosphorylation and Proteomics, Department of Cellular and Molecular Medicine, SyBioMa, KU Leuven, Leuven, BelgiumTranslational Cardiomyology Laboratory, Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven, Leuven, Belgium0Histology and Medical Embryology Unit, Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Sapienza University of Rome, Rome, ItalySkeletal muscle holds an intrinsic capability of growth and regeneration both in physiological conditions and in case of injury. Chronic muscle illnesses, generally caused by genetic and acquired factors, lead to deconditioning of the skeletal muscle structure and function, and are associated with a significant loss in muscle mass. At the same time, progressive muscle wasting is a hallmark of aging. Given the paracrine properties of myogenic stem cells, extracellular vesicle-derived signals have been studied for their potential implication in both the pathogenesis of degenerative neuromuscular diseases and as a possible therapeutic target. In this study, we screened the content of extracellular vesicles from animal models of muscle hypertrophy and muscle wasting associated with chronic disease and aging. Analysis of the transcriptome, protein cargo, and microRNAs (miRNAs) allowed us to identify a hypertrophic miRNA signature amenable for targeting muscle wasting, consisting of miR-1 and miR-208a. We tested this signature among others in vitro on mesoangioblasts (MABs), vessel-associated adult stem cells, and we observed an increase in the efficiency of myogenic differentiation. Furthermore, injections of miRNA-treated MABs in aged mice resulted in an improvement in skeletal muscle features, such as muscle weight, strength, cross-sectional area, and fibrosis compared to controls. Overall, we provide evidence that the extracellular vesicle-derived miRNA signature we identified enhances the myogenic potential of myogenic stem cells.https://www.frontiersin.org/articles/10.3389/fimmu.2022.977617/fullextracellular vesiclehypertrophymuscular dystrophyagingmiRNAskeletal muscle |
| spellingShingle | Laura Yedigaryan Ester Martínez-Sarrà Giorgia Giacomazzi Nefele Giarratana Bernard K. van der Veer Alessio Rotini Silvia Querceto Hanne Grosemans Álvaro Cortés-Calabuig Sara Salucci Michela Battistelli Elisabetta Falcieri Rik Gijsbers Mattia Quattrocelli Mattia Quattrocelli Kian Peng Koh Liesbeth De Waele Gunnar M. Buyse Rita Derua Maurilio Sampaolesi Maurilio Sampaolesi Extracellular vesicle-derived miRNAs improve stem cell-based therapeutic approaches in muscle wasting conditions Frontiers in Immunology extracellular vesicle hypertrophy muscular dystrophy aging miRNA skeletal muscle |
| title | Extracellular vesicle-derived miRNAs improve stem cell-based therapeutic approaches in muscle wasting conditions |
| title_full | Extracellular vesicle-derived miRNAs improve stem cell-based therapeutic approaches in muscle wasting conditions |
| title_fullStr | Extracellular vesicle-derived miRNAs improve stem cell-based therapeutic approaches in muscle wasting conditions |
| title_full_unstemmed | Extracellular vesicle-derived miRNAs improve stem cell-based therapeutic approaches in muscle wasting conditions |
| title_short | Extracellular vesicle-derived miRNAs improve stem cell-based therapeutic approaches in muscle wasting conditions |
| title_sort | extracellular vesicle derived mirnas improve stem cell based therapeutic approaches in muscle wasting conditions |
| topic | extracellular vesicle hypertrophy muscular dystrophy aging miRNA skeletal muscle |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.977617/full |
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