Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damage
BackgroundNeuropathic pain is one of the most difficult to treat chronic pain syndromes. It has significant effects on patients’ quality of life and substantially adds to the burden of direct and indirect medical costs. There is a critical need to improve therapies for peripheral nerve regeneration....
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-09-01
|
| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2022.992221/full |
| _version_ | 1798002016098713600 |
|---|---|
| author | Elsa González-Cubero María Luisa González-Fernández María Rodríguez-Díaz Marta Palomo-Irigoyen Marta Palomo-Irigoyen Ashwin Woodhoo Ashwin Woodhoo Ashwin Woodhoo Vega Villar-Suárez Vega Villar-Suárez |
| author_facet | Elsa González-Cubero María Luisa González-Fernández María Rodríguez-Díaz Marta Palomo-Irigoyen Marta Palomo-Irigoyen Ashwin Woodhoo Ashwin Woodhoo Ashwin Woodhoo Vega Villar-Suárez Vega Villar-Suárez |
| author_sort | Elsa González-Cubero |
| collection | DOAJ |
| description | BackgroundNeuropathic pain is one of the most difficult to treat chronic pain syndromes. It has significant effects on patients’ quality of life and substantially adds to the burden of direct and indirect medical costs. There is a critical need to improve therapies for peripheral nerve regeneration. The aim of this study is to address this issue by performing a detailed analysis of the therapeutic benefits of two treatment options: adipose tissue derived-mesenchymal stem cells (ASCs) and ASC-conditioned medium (CM).MethodsTo this end, we used an in vivo rat sciatic nerve damage model to investigate the molecular mechanisms involved in the myelinating capacity of ASCs and CM. Furthermore, effect of TNF and CM on Schwann cells (SCs) was evaluated. For our in vivo model, biomaterial surgical implants containing TNF were used to induce peripheral neuropathy in rats. Damaged nerves were also treated with either ASCs or CM and molecular methods were used to collect evidence of nerve regeneration. Post-operatively, rats were subjected to walking track analysis and their sciatic functional index was evaluated. Morphological data was gathered through transmission electron microscopy (TEM) of sciatic nerves harvested from the experimental rats. We also evaluated the effect of TNF on Schwann cells (SCs) in vitro. Genes and their correspondent proteins associated with nerve regeneration were analyzed by qPCR, western blot, and confocal microscopy.ResultsOur data suggests that both ASCs and CM are potentially beneficial treatments for promoting myelination and axonal regeneration. After TNF-induced nerve damage we observed an upregulation of c-Jun along with a downregulation of Krox-20 myelin-associated transcription factor. However, when CM was added to TNF-treated nerves the opposite effect occurred and also resulted in increased expression of myelin-related genes and their corresponding proteins.ConclusionFindings from our in vivo model showed that both ASCs and CM aided the regeneration of axonal myelin sheaths and the remodeling of peripheral nerve morphology. |
| first_indexed | 2024-04-11T11:46:40Z |
| format | Article |
| id | doaj.art-7881773875fc4fcf9fba6f276e5cc729 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-11T11:46:40Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-7881773875fc4fcf9fba6f276e5cc7292022-12-22T04:25:34ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022022-09-011610.3389/fncel.2022.992221992221Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damageElsa González-Cubero0María Luisa González-Fernández1María Rodríguez-Díaz2Marta Palomo-Irigoyen3Marta Palomo-Irigoyen4Ashwin Woodhoo5Ashwin Woodhoo6Ashwin Woodhoo7Vega Villar-Suárez8Vega Villar-Suárez9Department of Anatomy, Faculty of Veterinary Sciences, University of León-Universidad de León, León, SpainDepartment of Anatomy, Faculty of Veterinary Sciences, University of León-Universidad de León, León, SpainDepartment of Anatomy, Faculty of Veterinary Sciences, University of León-Universidad de León, León, SpainCenter for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, SpainGenes and Disease Group, Department of Dermatology, Medical University of Vienna, Anna Spiegel Center of Translational Research, Vienna, AustriaCenter for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, SpainIKERBASQUE, Basque Foundation for Science, Bilbao, SpainGene Regulatory Control in Disease Group, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, SpainDepartment of Anatomy, Faculty of Veterinary Sciences, University of León-Universidad de León, León, SpainInstitute of Biomedicine (IBIOMED), University of León-Universidad de León, León, SpainBackgroundNeuropathic pain is one of the most difficult to treat chronic pain syndromes. It has significant effects on patients’ quality of life and substantially adds to the burden of direct and indirect medical costs. There is a critical need to improve therapies for peripheral nerve regeneration. The aim of this study is to address this issue by performing a detailed analysis of the therapeutic benefits of two treatment options: adipose tissue derived-mesenchymal stem cells (ASCs) and ASC-conditioned medium (CM).MethodsTo this end, we used an in vivo rat sciatic nerve damage model to investigate the molecular mechanisms involved in the myelinating capacity of ASCs and CM. Furthermore, effect of TNF and CM on Schwann cells (SCs) was evaluated. For our in vivo model, biomaterial surgical implants containing TNF were used to induce peripheral neuropathy in rats. Damaged nerves were also treated with either ASCs or CM and molecular methods were used to collect evidence of nerve regeneration. Post-operatively, rats were subjected to walking track analysis and their sciatic functional index was evaluated. Morphological data was gathered through transmission electron microscopy (TEM) of sciatic nerves harvested from the experimental rats. We also evaluated the effect of TNF on Schwann cells (SCs) in vitro. Genes and their correspondent proteins associated with nerve regeneration were analyzed by qPCR, western blot, and confocal microscopy.ResultsOur data suggests that both ASCs and CM are potentially beneficial treatments for promoting myelination and axonal regeneration. After TNF-induced nerve damage we observed an upregulation of c-Jun along with a downregulation of Krox-20 myelin-associated transcription factor. However, when CM was added to TNF-treated nerves the opposite effect occurred and also resulted in increased expression of myelin-related genes and their corresponding proteins.ConclusionFindings from our in vivo model showed that both ASCs and CM aided the regeneration of axonal myelin sheaths and the remodeling of peripheral nerve morphology.https://www.frontiersin.org/articles/10.3389/fncel.2022.992221/fulladipose tissue derived-mesenchymal stem cellsSchwann cellsperipheral neuropathyconditioned mediumperipheral nerve regenerationnerve regeneration using mesenchymal stem cells |
| spellingShingle | Elsa González-Cubero María Luisa González-Fernández María Rodríguez-Díaz Marta Palomo-Irigoyen Marta Palomo-Irigoyen Ashwin Woodhoo Ashwin Woodhoo Ashwin Woodhoo Vega Villar-Suárez Vega Villar-Suárez Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damage Frontiers in Cellular Neuroscience adipose tissue derived-mesenchymal stem cells Schwann cells peripheral neuropathy conditioned medium peripheral nerve regeneration nerve regeneration using mesenchymal stem cells |
| title | Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damage |
| title_full | Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damage |
| title_fullStr | Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damage |
| title_full_unstemmed | Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damage |
| title_short | Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damage |
| title_sort | application of adipose derived mesenchymal stem cells in an in vivo model of peripheral nerve damage |
| topic | adipose tissue derived-mesenchymal stem cells Schwann cells peripheral neuropathy conditioned medium peripheral nerve regeneration nerve regeneration using mesenchymal stem cells |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2022.992221/full |
| work_keys_str_mv | AT elsagonzalezcubero applicationofadiposederivedmesenchymalstemcellsinaninvivomodelofperipheralnervedamage AT marialuisagonzalezfernandez applicationofadiposederivedmesenchymalstemcellsinaninvivomodelofperipheralnervedamage AT mariarodriguezdiaz applicationofadiposederivedmesenchymalstemcellsinaninvivomodelofperipheralnervedamage AT martapalomoirigoyen applicationofadiposederivedmesenchymalstemcellsinaninvivomodelofperipheralnervedamage AT martapalomoirigoyen applicationofadiposederivedmesenchymalstemcellsinaninvivomodelofperipheralnervedamage AT ashwinwoodhoo applicationofadiposederivedmesenchymalstemcellsinaninvivomodelofperipheralnervedamage AT ashwinwoodhoo applicationofadiposederivedmesenchymalstemcellsinaninvivomodelofperipheralnervedamage AT ashwinwoodhoo applicationofadiposederivedmesenchymalstemcellsinaninvivomodelofperipheralnervedamage AT vegavillarsuarez applicationofadiposederivedmesenchymalstemcellsinaninvivomodelofperipheralnervedamage AT vegavillarsuarez applicationofadiposederivedmesenchymalstemcellsinaninvivomodelofperipheralnervedamage |