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Neurotrophic support by traumatized muscle-derived multipotent progenitor cells: Role of endothelial cells and Vascular Endothelial Growth Factor-A
BACKGROUND: Adult mesenchymal stem cells (MSCs) have been shown to increase nerve regeneration in animal models of nerve injury. Traumatized muscle-derived multipotent progenitor cells (MPCs) share important characteristics with MSCs and are isolated from severely damaged muscle tissue following sur...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640955/ https://www.ncbi.nlm.nih.gov/pubmed/29029631 http://dx.doi.org/10.1186/s13287-017-0665-4 |
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author | Zupanc, Heidi R. H. Alexander, Peter G. Tuan, Rocky S. |
author_facet | Zupanc, Heidi R. H. Alexander, Peter G. Tuan, Rocky S. |
author_sort | Zupanc, Heidi R. H. |
collection | PubMed |
description | BACKGROUND: Adult mesenchymal stem cells (MSCs) have been shown to increase nerve regeneration in animal models of nerve injury. Traumatized muscle-derived multipotent progenitor cells (MPCs) share important characteristics with MSCs and are isolated from severely damaged muscle tissue following surgical debridement. Previous investigations have shown that MPCs may be induced to increase production of several neurotrophic factors, suggesting the possible utility of autologous MPCs in peripheral nerve regeneration following injury. Recent findings have also shown that components of the vascular niche, including endothelial cells (ECs) and vascular endothelial growth factor (VEGF)-A, regulate neural progenitor cells and sensory neurons. METHODS: In this study, we have investigated the neuroinductive activities of MPCs, particularly MPC-produced VEGF-A, in the context of an aligned, neuroconductive nerve guide conduit and the endothelial component of the vascular system. Embryonic dorsal root ganglia (DRG) seeded on poly-ϵ-caprolactone aligned nanofibrous scaffold (NF) constructs and on tissue culture plastic, were cocultured with induced MPCs or treated with their conditioned medium (MPC-CM). RESULTS: Increased neurite extension was observed on both NF and tissue culture plastic in the presence of MPC-CM versus cell-free control CM. The addition of CM from ECs significantly increased the neurotrophic activity of induced MPC-CM, suggesting that MPC and EC neurotrophic activity may be synergistic. Distinctly higher VEGF-A production was seen in MPCs following neurotrophic induction versus culture under normal growth conditions. Selective removal of VEGF-A from MPC-CM reduced the observed DRG neurite extension length, indicating VEGF-A involvement in neurotrophic activity of the CM. CONCLUSIONS: Taken together, these findings suggest the potential of MPCs to encourage nerve growth via a VEGF-A-dependent action, and the use of MPC-CM or a combination of MPC and CM from ECs for peripheral nerve repair in conjunction with NFs in a nerve guide conduit. Due to the ease of use, application of bioactive agents derived from cultured cells to enhance neurotrophic support presents a promising line of research into peripheral nerve repair. |
format | Online Article Text |
id | pubmed-5640955 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-56409552017-10-18 Neurotrophic support by traumatized muscle-derived multipotent progenitor cells: Role of endothelial cells and Vascular Endothelial Growth Factor-A Zupanc, Heidi R. H. Alexander, Peter G. Tuan, Rocky S. Stem Cell Res Ther Research BACKGROUND: Adult mesenchymal stem cells (MSCs) have been shown to increase nerve regeneration in animal models of nerve injury. Traumatized muscle-derived multipotent progenitor cells (MPCs) share important characteristics with MSCs and are isolated from severely damaged muscle tissue following surgical debridement. Previous investigations have shown that MPCs may be induced to increase production of several neurotrophic factors, suggesting the possible utility of autologous MPCs in peripheral nerve regeneration following injury. Recent findings have also shown that components of the vascular niche, including endothelial cells (ECs) and vascular endothelial growth factor (VEGF)-A, regulate neural progenitor cells and sensory neurons. METHODS: In this study, we have investigated the neuroinductive activities of MPCs, particularly MPC-produced VEGF-A, in the context of an aligned, neuroconductive nerve guide conduit and the endothelial component of the vascular system. Embryonic dorsal root ganglia (DRG) seeded on poly-ϵ-caprolactone aligned nanofibrous scaffold (NF) constructs and on tissue culture plastic, were cocultured with induced MPCs or treated with their conditioned medium (MPC-CM). RESULTS: Increased neurite extension was observed on both NF and tissue culture plastic in the presence of MPC-CM versus cell-free control CM. The addition of CM from ECs significantly increased the neurotrophic activity of induced MPC-CM, suggesting that MPC and EC neurotrophic activity may be synergistic. Distinctly higher VEGF-A production was seen in MPCs following neurotrophic induction versus culture under normal growth conditions. Selective removal of VEGF-A from MPC-CM reduced the observed DRG neurite extension length, indicating VEGF-A involvement in neurotrophic activity of the CM. CONCLUSIONS: Taken together, these findings suggest the potential of MPCs to encourage nerve growth via a VEGF-A-dependent action, and the use of MPC-CM or a combination of MPC and CM from ECs for peripheral nerve repair in conjunction with NFs in a nerve guide conduit. Due to the ease of use, application of bioactive agents derived from cultured cells to enhance neurotrophic support presents a promising line of research into peripheral nerve repair. BioMed Central 2017-10-13 /pmc/articles/PMC5640955/ /pubmed/29029631 http://dx.doi.org/10.1186/s13287-017-0665-4 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Zupanc, Heidi R. H. Alexander, Peter G. Tuan, Rocky S. Neurotrophic support by traumatized muscle-derived multipotent progenitor cells: Role of endothelial cells and Vascular Endothelial Growth Factor-A |
title | Neurotrophic support by traumatized muscle-derived multipotent progenitor cells: Role of endothelial cells and Vascular Endothelial Growth Factor-A |
title_full | Neurotrophic support by traumatized muscle-derived multipotent progenitor cells: Role of endothelial cells and Vascular Endothelial Growth Factor-A |
title_fullStr | Neurotrophic support by traumatized muscle-derived multipotent progenitor cells: Role of endothelial cells and Vascular Endothelial Growth Factor-A |
title_full_unstemmed | Neurotrophic support by traumatized muscle-derived multipotent progenitor cells: Role of endothelial cells and Vascular Endothelial Growth Factor-A |
title_short | Neurotrophic support by traumatized muscle-derived multipotent progenitor cells: Role of endothelial cells and Vascular Endothelial Growth Factor-A |
title_sort | neurotrophic support by traumatized muscle-derived multipotent progenitor cells: role of endothelial cells and vascular endothelial growth factor-a |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640955/ https://www.ncbi.nlm.nih.gov/pubmed/29029631 http://dx.doi.org/10.1186/s13287-017-0665-4 |
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