Physiactisome: A New Nanovesicle Drug Containing Heat Shock Protein 60 for Treating Muscle Wasting and Cachexia
Currently, no commercially available drugs have the ability to reverse cachexia or counteract muscle wasting and the loss of lean mass. Here, we report the methodology used to develop Physiactisome—a conditioned medium released by heat shock protein 60 (Hsp60)—overexpressing C2C12 cell lines enriche...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/9/1406 |
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| author | Valentina Di Felice Rosario Barone Eleonora Trovato Daniela D’Amico Filippo Macaluso Claudia Campanella Antonella Marino Gammazza Vera Muccilli Vincenzo Cunsolo Patrizia Cancemi Gabriele Multhoff Dario Coletti Sergio Adamo Felicia Farina Francesco Cappello |
| author_facet | Valentina Di Felice Rosario Barone Eleonora Trovato Daniela D’Amico Filippo Macaluso Claudia Campanella Antonella Marino Gammazza Vera Muccilli Vincenzo Cunsolo Patrizia Cancemi Gabriele Multhoff Dario Coletti Sergio Adamo Felicia Farina Francesco Cappello |
| author_sort | Valentina Di Felice |
| collection | DOAJ |
| description | Currently, no commercially available drugs have the ability to reverse cachexia or counteract muscle wasting and the loss of lean mass. Here, we report the methodology used to develop Physiactisome—a conditioned medium released by heat shock protein 60 (Hsp60)—overexpressing C2C12 cell lines enriched with small and large extracellular vesicles. We also present evidence supporting its use in the treatment of cachexia. Briefly, we obtain a nanovesicle-based secretion by genetically modifying C2C12 cell lines with an <i>Hsp60</i>-overexpressing plasmid. The secretion is used to treat naïve C2C12 cell lines. Physiactisome activates the expression of PGC-1α isoform 1, which is directly involved in mitochondrial biogenesis and muscle atrophy suppression, in naïve C2C12 cell lines. Proteomic analyses show Hsp60 localisation inside isolated nanovesicles and the localisation of several apocrine and merocrine molecules, with potential benefits for severe forms of muscle atrophy. Considering that Physiactisome can be easily obtained following tissue biopsy and can be applied to autologous muscle stem cells, we propose a potential nanovesicle-based anti-cachexia drug that could mimic the beneficial effects of exercise. Thus, Physiactisome may improve patient survival and quality of life. Furthermore, the method used to add Hsp60 into nanovesicles can be used to deliver other drugs or active proteins to vesicles. |
| first_indexed | 2024-03-10T04:17:14Z |
| format | Article |
| id | doaj.art-a6fd71659ea948c09164606318511f7e |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T04:17:14Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-a6fd71659ea948c09164606318511f7e2023-11-23T07:58:47ZengMDPI AGCells2073-44092022-04-01119140610.3390/cells11091406Physiactisome: A New Nanovesicle Drug Containing Heat Shock Protein 60 for Treating Muscle Wasting and CachexiaValentina Di Felice0Rosario Barone1Eleonora Trovato2Daniela D’Amico3Filippo Macaluso4Claudia Campanella5Antonella Marino Gammazza6Vera Muccilli7Vincenzo Cunsolo8Patrizia Cancemi9Gabriele Multhoff10Dario Coletti11Sergio Adamo12Felicia Farina13Francesco Cappello14Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, ItalyDepartment of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, ItalyDepartment of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, ItalyDepartment of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, ItalySMART Engineering Solutions & Technologies Research Center, eCampus University, 22160 Novedrate, ItalyDepartment of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, ItalyDepartment of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, ItalyDepartment of Chemical Sciences, University of Catania, 95129 Catania, ItalyDepartment of Chemical Sciences, University of Catania, 95129 Catania, ItalyDepartment of Biological Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90127 Palermo, ItalyDepartment of Radiation Oncology, School of Medicine, Central Institute for Translational Cancer Research, Technical University of Munich, TranslaTUM, 80333 Munich, GermanyDAHFMO Unit of Histology and Medical Embryology, Sapienza University of Rome, 00185 Rome, ItalyDAHFMO Unit of Histology and Medical Embryology, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, ItalyDepartment of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, ItalyCurrently, no commercially available drugs have the ability to reverse cachexia or counteract muscle wasting and the loss of lean mass. Here, we report the methodology used to develop Physiactisome—a conditioned medium released by heat shock protein 60 (Hsp60)—overexpressing C2C12 cell lines enriched with small and large extracellular vesicles. We also present evidence supporting its use in the treatment of cachexia. Briefly, we obtain a nanovesicle-based secretion by genetically modifying C2C12 cell lines with an <i>Hsp60</i>-overexpressing plasmid. The secretion is used to treat naïve C2C12 cell lines. Physiactisome activates the expression of PGC-1α isoform 1, which is directly involved in mitochondrial biogenesis and muscle atrophy suppression, in naïve C2C12 cell lines. Proteomic analyses show Hsp60 localisation inside isolated nanovesicles and the localisation of several apocrine and merocrine molecules, with potential benefits for severe forms of muscle atrophy. Considering that Physiactisome can be easily obtained following tissue biopsy and can be applied to autologous muscle stem cells, we propose a potential nanovesicle-based anti-cachexia drug that could mimic the beneficial effects of exercise. Thus, Physiactisome may improve patient survival and quality of life. Furthermore, the method used to add Hsp60 into nanovesicles can be used to deliver other drugs or active proteins to vesicles.https://www.mdpi.com/2073-4409/11/9/1406cachexiamuscle atrophyexerciseexosomemuscle wastingsarcopenia |
| spellingShingle | Valentina Di Felice Rosario Barone Eleonora Trovato Daniela D’Amico Filippo Macaluso Claudia Campanella Antonella Marino Gammazza Vera Muccilli Vincenzo Cunsolo Patrizia Cancemi Gabriele Multhoff Dario Coletti Sergio Adamo Felicia Farina Francesco Cappello Physiactisome: A New Nanovesicle Drug Containing Heat Shock Protein 60 for Treating Muscle Wasting and Cachexia Cells cachexia muscle atrophy exercise exosome muscle wasting sarcopenia |
| title | Physiactisome: A New Nanovesicle Drug Containing Heat Shock Protein 60 for Treating Muscle Wasting and Cachexia |
| title_full | Physiactisome: A New Nanovesicle Drug Containing Heat Shock Protein 60 for Treating Muscle Wasting and Cachexia |
| title_fullStr | Physiactisome: A New Nanovesicle Drug Containing Heat Shock Protein 60 for Treating Muscle Wasting and Cachexia |
| title_full_unstemmed | Physiactisome: A New Nanovesicle Drug Containing Heat Shock Protein 60 for Treating Muscle Wasting and Cachexia |
| title_short | Physiactisome: A New Nanovesicle Drug Containing Heat Shock Protein 60 for Treating Muscle Wasting and Cachexia |
| title_sort | physiactisome a new nanovesicle drug containing heat shock protein 60 for treating muscle wasting and cachexia |
| topic | cachexia muscle atrophy exercise exosome muscle wasting sarcopenia |
| url | https://www.mdpi.com/2073-4409/11/9/1406 |
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