Decellularized skeletal muscles display neurotrophic effects in three‐dimensional organotypic cultures
Abstract Skeletal muscle decellularization allows the generation of natural scaffolds that retain the extracellular matrix (ECM) mechanical integrity, biological activity, and three‐dimensional (3D) architecture of the native tissue. Recent reports showed that in vivo implantation of decellularized...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Oxford University Press
2020-10-01
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| Series: | Stem Cells Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/sctm.20-0090 |
| _version_ | 1818907046105317376 |
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| author | Paolo Raffa Valentina Scattolini Mattia Francesco Maria Gerli Silvia Perin Meihua Cui Paolo De Coppi Nicola Elvassore Paola Caccin Camilla Luni Anna Urciuolo |
| author_facet | Paolo Raffa Valentina Scattolini Mattia Francesco Maria Gerli Silvia Perin Meihua Cui Paolo De Coppi Nicola Elvassore Paola Caccin Camilla Luni Anna Urciuolo |
| author_sort | Paolo Raffa |
| collection | DOAJ |
| description | Abstract Skeletal muscle decellularization allows the generation of natural scaffolds that retain the extracellular matrix (ECM) mechanical integrity, biological activity, and three‐dimensional (3D) architecture of the native tissue. Recent reports showed that in vivo implantation of decellularized muscles supports muscle regeneration in volumetric muscle loss models, including nervous system and neuromuscular junctional homing. Since the nervous system plays pivotal roles during skeletal muscle regeneration and in tissue homeostasis, support of reinnervation is a crucial aspect to be considered. However, the effect of decellularized muscles on reinnervation and on neuronal axon growth has been poorly investigated. Here, we characterized residual protein composition of decellularized muscles by mass spectrometry and we show that scaffolds preserve structural proteins of the ECM of both skeletal muscle and peripheral nervous system. To investigate whether decellularized scaffolds could per se attract neural axons, organotypic sections of spinal cord were cultured three dimensionally in vitro, in presence or in absence of decellularized muscles. We found that neural axons extended from the spinal cord are attracted by the decellularized muscles and penetrate inside the scaffolds upon 3D coculture. These results demonstrate that decellularized scaffolds possess intrinsic neurotrophic properties, supporting their potential use for the treatment of clinical cases where extensive functional regeneration of the muscle is required. |
| first_indexed | 2024-12-19T21:48:53Z |
| format | Article |
| id | doaj.art-2958a840477c4d71a2a6a195d6d1d41a |
| institution | Directory Open Access Journal |
| issn | 2157-6564 2157-6580 |
| language | English |
| last_indexed | 2024-12-19T21:48:53Z |
| publishDate | 2020-10-01 |
| publisher | Oxford University Press |
| record_format | Article |
| series | Stem Cells Translational Medicine |
| spelling | doaj.art-2958a840477c4d71a2a6a195d6d1d41a2022-12-21T20:04:27ZengOxford University PressStem Cells Translational Medicine2157-65642157-65802020-10-019101233124310.1002/sctm.20-0090Decellularized skeletal muscles display neurotrophic effects in three‐dimensional organotypic culturesPaolo Raffa0Valentina Scattolini1Mattia Francesco Maria Gerli2Silvia Perin3Meihua Cui4Paolo De Coppi5Nicola Elvassore6Paola Caccin7Camilla Luni8Anna Urciuolo9Veneto Institute of Molecular Medicine Padova ItalyVeneto Institute of Molecular Medicine Padova ItalyUniversity College London Great Ormond Street Institute of Child Health London UKUniversity College London Great Ormond Street Institute of Child Health London UKShanghai Institute for Advanced Immunochemical Studies (SIAIS) ShanghaiTech University Shanghai People's Republic of ChinaUniversity College London Great Ormond Street Institute of Child Health London UKVeneto Institute of Molecular Medicine Padova ItalyBiomedical Science Department University of Padova Padova ItalyShanghai Institute for Advanced Immunochemical Studies (SIAIS) ShanghaiTech University Shanghai People's Republic of ChinaUniversity College London Great Ormond Street Institute of Child Health London UKAbstract Skeletal muscle decellularization allows the generation of natural scaffolds that retain the extracellular matrix (ECM) mechanical integrity, biological activity, and three‐dimensional (3D) architecture of the native tissue. Recent reports showed that in vivo implantation of decellularized muscles supports muscle regeneration in volumetric muscle loss models, including nervous system and neuromuscular junctional homing. Since the nervous system plays pivotal roles during skeletal muscle regeneration and in tissue homeostasis, support of reinnervation is a crucial aspect to be considered. However, the effect of decellularized muscles on reinnervation and on neuronal axon growth has been poorly investigated. Here, we characterized residual protein composition of decellularized muscles by mass spectrometry and we show that scaffolds preserve structural proteins of the ECM of both skeletal muscle and peripheral nervous system. To investigate whether decellularized scaffolds could per se attract neural axons, organotypic sections of spinal cord were cultured three dimensionally in vitro, in presence or in absence of decellularized muscles. We found that neural axons extended from the spinal cord are attracted by the decellularized muscles and penetrate inside the scaffolds upon 3D coculture. These results demonstrate that decellularized scaffolds possess intrinsic neurotrophic properties, supporting their potential use for the treatment of clinical cases where extensive functional regeneration of the muscle is required.https://doi.org/10.1002/sctm.20-00903D cultureaxonsdecellularized muscleECMinnervationneurons |
| spellingShingle | Paolo Raffa Valentina Scattolini Mattia Francesco Maria Gerli Silvia Perin Meihua Cui Paolo De Coppi Nicola Elvassore Paola Caccin Camilla Luni Anna Urciuolo Decellularized skeletal muscles display neurotrophic effects in three‐dimensional organotypic cultures Stem Cells Translational Medicine 3D culture axons decellularized muscle ECM innervation neurons |
| title | Decellularized skeletal muscles display neurotrophic effects in three‐dimensional organotypic cultures |
| title_full | Decellularized skeletal muscles display neurotrophic effects in three‐dimensional organotypic cultures |
| title_fullStr | Decellularized skeletal muscles display neurotrophic effects in three‐dimensional organotypic cultures |
| title_full_unstemmed | Decellularized skeletal muscles display neurotrophic effects in three‐dimensional organotypic cultures |
| title_short | Decellularized skeletal muscles display neurotrophic effects in three‐dimensional organotypic cultures |
| title_sort | decellularized skeletal muscles display neurotrophic effects in three dimensional organotypic cultures |
| topic | 3D culture axons decellularized muscle ECM innervation neurons |
| url | https://doi.org/10.1002/sctm.20-0090 |
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