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Autologous Bone Marrow Mesenchymal Stem Cells Improve the Quality and Stability of Vascularized Flap Surgery of Irradiated Skin in Pigs
Cutaneous radiation syndrome has severe long‐term health consequences. Because it causes an unpredictable course of inflammatory waves, conventional surgical treatment is ineffective and often leads to a fibronecrotic process. Data about the long‐term stability of healed wounds, with neither inflamm...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090511/ https://www.ncbi.nlm.nih.gov/pubmed/29777577 http://dx.doi.org/10.1002/sctm.17-0267 |
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author | Linard, Christine Brachet, Michel Strup‐Perrot, Carine L'homme, Bruno Busson, Elodie Squiban, Claire Holler, Valerie Bonneau, Michel Lataillade, Jean‐Jacques Bey, Eric Benderitter, Marc |
author_facet | Linard, Christine Brachet, Michel Strup‐Perrot, Carine L'homme, Bruno Busson, Elodie Squiban, Claire Holler, Valerie Bonneau, Michel Lataillade, Jean‐Jacques Bey, Eric Benderitter, Marc |
author_sort | Linard, Christine |
collection | PubMed |
description | Cutaneous radiation syndrome has severe long‐term health consequences. Because it causes an unpredictable course of inflammatory waves, conventional surgical treatment is ineffective and often leads to a fibronecrotic process. Data about the long‐term stability of healed wounds, with neither inflammation nor resumption of fibrosis, are lacking. In this study, we investigated the effect of injections of local autologous bone marrow‐derived mesenchymal stromal cells (BM‐MSCs), combined with plastic surgery for skin necrosis, in a large‐animal model. Three months after irradiation overexposure to the rump, minipigs were divided into three groups: one group treated by simple excision of the necrotic tissue, the second by vascularized‐flap surgery, and the third by vascularized‐flap surgery and local autologous BM‐MSC injections. Three additional injections of the BM‐MSCs were performed weekly for 3 weeks. The quality of cutaneous wound healing was examined 1 year post‐treatment. The necrotic tissue excision induced a pathologic scar characterized by myofibroblasts, excessive collagen‐1 deposits, and inadequate vascular density. The vascularized‐flap surgery alone was accompanied by inadequate production of extracellular matrix (ECM) proteins (decorin, fibronectin); the low col1/col3 ratio, associated with persistent inflammatory nodules, and the loss of vascularization both attested to continued immaturity of the ECM. BM‐MSC therapy combined with vascularized‐flap surgery provided mature wound healing characterized by a col1/col3 ratio and decorin and fibronectin expression that were all similar to that of nonirradiated skin, with no inflammation, and vascular stability. In this preclinical model, vascularized flap surgery successfully and lastingly remodeled irradiated skin only when combined with BM‐MSC therapy. Stem Cells Translational Medicine 2018:569–582 |
format | Online Article Text |
id | pubmed-6090511 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60905112018-08-17 Autologous Bone Marrow Mesenchymal Stem Cells Improve the Quality and Stability of Vascularized Flap Surgery of Irradiated Skin in Pigs Linard, Christine Brachet, Michel Strup‐Perrot, Carine L'homme, Bruno Busson, Elodie Squiban, Claire Holler, Valerie Bonneau, Michel Lataillade, Jean‐Jacques Bey, Eric Benderitter, Marc Stem Cells Transl Med Translational Research Articles and Reviews Cutaneous radiation syndrome has severe long‐term health consequences. Because it causes an unpredictable course of inflammatory waves, conventional surgical treatment is ineffective and often leads to a fibronecrotic process. Data about the long‐term stability of healed wounds, with neither inflammation nor resumption of fibrosis, are lacking. In this study, we investigated the effect of injections of local autologous bone marrow‐derived mesenchymal stromal cells (BM‐MSCs), combined with plastic surgery for skin necrosis, in a large‐animal model. Three months after irradiation overexposure to the rump, minipigs were divided into three groups: one group treated by simple excision of the necrotic tissue, the second by vascularized‐flap surgery, and the third by vascularized‐flap surgery and local autologous BM‐MSC injections. Three additional injections of the BM‐MSCs were performed weekly for 3 weeks. The quality of cutaneous wound healing was examined 1 year post‐treatment. The necrotic tissue excision induced a pathologic scar characterized by myofibroblasts, excessive collagen‐1 deposits, and inadequate vascular density. The vascularized‐flap surgery alone was accompanied by inadequate production of extracellular matrix (ECM) proteins (decorin, fibronectin); the low col1/col3 ratio, associated with persistent inflammatory nodules, and the loss of vascularization both attested to continued immaturity of the ECM. BM‐MSC therapy combined with vascularized‐flap surgery provided mature wound healing characterized by a col1/col3 ratio and decorin and fibronectin expression that were all similar to that of nonirradiated skin, with no inflammation, and vascular stability. In this preclinical model, vascularized flap surgery successfully and lastingly remodeled irradiated skin only when combined with BM‐MSC therapy. Stem Cells Translational Medicine 2018:569–582 John Wiley and Sons Inc. 2018-05-18 /pmc/articles/PMC6090511/ /pubmed/29777577 http://dx.doi.org/10.1002/sctm.17-0267 Text en © 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Translational Research Articles and Reviews Linard, Christine Brachet, Michel Strup‐Perrot, Carine L'homme, Bruno Busson, Elodie Squiban, Claire Holler, Valerie Bonneau, Michel Lataillade, Jean‐Jacques Bey, Eric Benderitter, Marc Autologous Bone Marrow Mesenchymal Stem Cells Improve the Quality and Stability of Vascularized Flap Surgery of Irradiated Skin in Pigs |
title | Autologous Bone Marrow Mesenchymal Stem Cells Improve the Quality and Stability of Vascularized Flap Surgery of Irradiated Skin in Pigs |
title_full | Autologous Bone Marrow Mesenchymal Stem Cells Improve the Quality and Stability of Vascularized Flap Surgery of Irradiated Skin in Pigs |
title_fullStr | Autologous Bone Marrow Mesenchymal Stem Cells Improve the Quality and Stability of Vascularized Flap Surgery of Irradiated Skin in Pigs |
title_full_unstemmed | Autologous Bone Marrow Mesenchymal Stem Cells Improve the Quality and Stability of Vascularized Flap Surgery of Irradiated Skin in Pigs |
title_short | Autologous Bone Marrow Mesenchymal Stem Cells Improve the Quality and Stability of Vascularized Flap Surgery of Irradiated Skin in Pigs |
title_sort | autologous bone marrow mesenchymal stem cells improve the quality and stability of vascularized flap surgery of irradiated skin in pigs |
topic | Translational Research Articles and Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090511/ https://www.ncbi.nlm.nih.gov/pubmed/29777577 http://dx.doi.org/10.1002/sctm.17-0267 |
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