Sutures enriched with adipose-derived stem cells decrease the local acute inflammation after tracheal anastomosis in a murine model

OBJECTIVES Local inflammatory reaction and tension are the main causes of postoperative complications after tracheal surgery. Adipose-derived stem cells (ASCs) are known to have immunomodulatory activity. The exact mechanism of this activity is not known, although it is possible that they modulate t...

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Veröffentlicht in:European journal of cardio-thoracic surgery 2012-09, Vol.42 (3), p.e40-e47
Hauptverfasser: Georgiev-Hristov, Tihomir, García-Arranz, Mariano, García-Gómez, Ignacio, García-Cabezas, Miguel Angel, Trébol, Jacobo, Vega-Clemente, Luz, Díaz-Agero, Prudencio, García-Olmo, Damián
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container_title European journal of cardio-thoracic surgery
container_volume 42
creator Georgiev-Hristov, Tihomir
García-Arranz, Mariano
García-Gómez, Ignacio
García-Cabezas, Miguel Angel
Trébol, Jacobo
Vega-Clemente, Luz
Díaz-Agero, Prudencio
García-Olmo, Damián
description OBJECTIVES Local inflammatory reaction and tension are the main causes of postoperative complications after tracheal surgery. Adipose-derived stem cells (ASCs) are known to have immunomodulatory activity. The exact mechanism of this activity is not known, although it is possible that they modulate the function of different cells involved in the immune response. Little is known of their impact on acute inflammation, especially in the problematic tracheal area. We aimed to study the effect of ASCs applied locally in an animal model of tracheal resection and anastomosis. METHODS ASCs from the subcutaneous fat of BDIX rats were infected for expression of the enhanced green fluorescent protein (eGFP) and were cultured with Polyglactin 910 sutures to obtain biosutures (ASC-coated sutures). After tracheal resection, 90 BDIX rats (syngeneic, autologous model) underwent anastomosis with biosutures (1.5 × 106 cells/biosuture [Group 1] or 0.5 × 106 cells/biosuture [Group 2]) or conventional sutures (Group 3). The animals were killed after 1, 4, 10, 30 or 60 days and histological and immunofluorescence studies were performed on the anastomotic areas. Inflammatory cell densities were graded semiquantitatively by the pathologist in a blinded fashion. RESULTS In the early period (1 and 4 days), the biosuture groups presented an atypical pattern of acute inflammation, characterized by the almost complete absence of neutrophils, and the presence of abundant lymphocytes and plasma cells, compared with the control group (P < 0.05). Moreover, abundant macrophages/monocytes were immunolocated around blood vessels near the biosutures and between biosuture threads 1 day after anastomosis, whereas the presence of macrophages/monocytes in animals treated with conventional sutures was discrete (P < 0.05). No differences were observed in the later period. No side effects in the biosuture groups were found. CONCLUSIONS Biosutures are a comfortable way of stem cell delivery to the surgical field without modification of the operative protocol. ASCs suppress the local acute inflammatory reaction (increased macrophage migration and decreased neutrophil infiltration) in the tracheal anastomosis and cause an early switch from acute to chronic inflammation.
doi_str_mv 10.1093/ejcts/ezs357
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Adipose-derived stem cells (ASCs) are known to have immunomodulatory activity. The exact mechanism of this activity is not known, although it is possible that they modulate the function of different cells involved in the immune response. Little is known of their impact on acute inflammation, especially in the problematic tracheal area. We aimed to study the effect of ASCs applied locally in an animal model of tracheal resection and anastomosis. METHODS ASCs from the subcutaneous fat of BDIX rats were infected for expression of the enhanced green fluorescent protein (eGFP) and were cultured with Polyglactin 910 sutures to obtain biosutures (ASC-coated sutures). After tracheal resection, 90 BDIX rats (syngeneic, autologous model) underwent anastomosis with biosutures (1.5 × 106 cells/biosuture [Group 1] or 0.5 × 106 cells/biosuture [Group 2]) or conventional sutures (Group 3). The animals were killed after 1, 4, 10, 30 or 60 days and histological and immunofluorescence studies were performed on the anastomotic areas. Inflammatory cell densities were graded semiquantitatively by the pathologist in a blinded fashion. RESULTS In the early period (1 and 4 days), the biosuture groups presented an atypical pattern of acute inflammation, characterized by the almost complete absence of neutrophils, and the presence of abundant lymphocytes and plasma cells, compared with the control group (P &lt; 0.05). Moreover, abundant macrophages/monocytes were immunolocated around blood vessels near the biosutures and between biosuture threads 1 day after anastomosis, whereas the presence of macrophages/monocytes in animals treated with conventional sutures was discrete (P &lt; 0.05). No differences were observed in the later period. No side effects in the biosuture groups were found. CONCLUSIONS Biosutures are a comfortable way of stem cell delivery to the surgical field without modification of the operative protocol. ASCs suppress the local acute inflammatory reaction (increased macrophage migration and decreased neutrophil infiltration) in the tracheal anastomosis and cause an early switch from acute to chronic inflammation.</description><identifier>ISSN: 1010-7940</identifier><identifier>EISSN: 1873-734X</identifier><identifier>DOI: 10.1093/ejcts/ezs357</identifier><identifier>PMID: 22689184</identifier><language>eng</language><publisher>Germany: Oxford University Press</publisher><subject>Adipose Tissue ; Anastomosis, Surgical - methods ; Animals ; Bioprosthesis ; Disease Models, Animal ; Flow Cytometry ; Immunohistochemistry ; Inflammation - prevention &amp; control ; Male ; Mesenchymal Stem Cell Transplantation ; Postoperative Complications - prevention &amp; control ; Random Allocation ; Rats ; Rats, Inbred Strains ; Sensitivity and Specificity ; Statistics, Nonparametric ; Suture Techniques ; Sutures ; Trachea - pathology ; Trachea - surgery ; Tracheotomy - methods ; Treatment Outcome</subject><ispartof>European journal of cardio-thoracic surgery, 2012-09, Vol.42 (3), p.e40-e47</ispartof><rights>The Author 2012. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c361t-5088d4e8e129f9b9df1f6ef4fee0bf13bcb9100c00dca0c9fce1f7a27114c49a3</citedby><cites>FETCH-LOGICAL-c361t-5088d4e8e129f9b9df1f6ef4fee0bf13bcb9100c00dca0c9fce1f7a27114c49a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22689184$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Georgiev-Hristov, Tihomir</creatorcontrib><creatorcontrib>García-Arranz, Mariano</creatorcontrib><creatorcontrib>García-Gómez, Ignacio</creatorcontrib><creatorcontrib>García-Cabezas, Miguel Angel</creatorcontrib><creatorcontrib>Trébol, Jacobo</creatorcontrib><creatorcontrib>Vega-Clemente, Luz</creatorcontrib><creatorcontrib>Díaz-Agero, Prudencio</creatorcontrib><creatorcontrib>García-Olmo, Damián</creatorcontrib><title>Sutures enriched with adipose-derived stem cells decrease the local acute inflammation after tracheal anastomosis in a murine model</title><title>European journal of cardio-thoracic surgery</title><addtitle>Eur J Cardiothorac Surg</addtitle><description>OBJECTIVES Local inflammatory reaction and tension are the main causes of postoperative complications after tracheal surgery. Adipose-derived stem cells (ASCs) are known to have immunomodulatory activity. The exact mechanism of this activity is not known, although it is possible that they modulate the function of different cells involved in the immune response. Little is known of their impact on acute inflammation, especially in the problematic tracheal area. We aimed to study the effect of ASCs applied locally in an animal model of tracheal resection and anastomosis. METHODS ASCs from the subcutaneous fat of BDIX rats were infected for expression of the enhanced green fluorescent protein (eGFP) and were cultured with Polyglactin 910 sutures to obtain biosutures (ASC-coated sutures). After tracheal resection, 90 BDIX rats (syngeneic, autologous model) underwent anastomosis with biosutures (1.5 × 106 cells/biosuture [Group 1] or 0.5 × 106 cells/biosuture [Group 2]) or conventional sutures (Group 3). The animals were killed after 1, 4, 10, 30 or 60 days and histological and immunofluorescence studies were performed on the anastomotic areas. Inflammatory cell densities were graded semiquantitatively by the pathologist in a blinded fashion. RESULTS In the early period (1 and 4 days), the biosuture groups presented an atypical pattern of acute inflammation, characterized by the almost complete absence of neutrophils, and the presence of abundant lymphocytes and plasma cells, compared with the control group (P &lt; 0.05). Moreover, abundant macrophages/monocytes were immunolocated around blood vessels near the biosutures and between biosuture threads 1 day after anastomosis, whereas the presence of macrophages/monocytes in animals treated with conventional sutures was discrete (P &lt; 0.05). No differences were observed in the later period. No side effects in the biosuture groups were found. CONCLUSIONS Biosutures are a comfortable way of stem cell delivery to the surgical field without modification of the operative protocol. ASCs suppress the local acute inflammatory reaction (increased macrophage migration and decreased neutrophil infiltration) in the tracheal anastomosis and cause an early switch from acute to chronic inflammation.</description><subject>Adipose Tissue</subject><subject>Anastomosis, Surgical - methods</subject><subject>Animals</subject><subject>Bioprosthesis</subject><subject>Disease Models, Animal</subject><subject>Flow Cytometry</subject><subject>Immunohistochemistry</subject><subject>Inflammation - prevention &amp; control</subject><subject>Male</subject><subject>Mesenchymal Stem Cell Transplantation</subject><subject>Postoperative Complications - prevention &amp; control</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Sensitivity and Specificity</subject><subject>Statistics, Nonparametric</subject><subject>Suture Techniques</subject><subject>Sutures</subject><subject>Trachea - pathology</subject><subject>Trachea - surgery</subject><subject>Tracheotomy - methods</subject><subject>Treatment Outcome</subject><issn>1010-7940</issn><issn>1873-734X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90D1LBDEQBuAgit-dtaTTwtVkk7vdlHL4BYKFCnZLNplwkc3mzGQVbf3j7nlqaTXD8PDCvIQccHbKmRJn8GwynsEHikm1RrZ5XYmiEvJpfdwZZ0WlJNsiO4jPjLGpKKtNslWW01rxWm6Tz_shDwmQQp-8mYOlbz7PqbZ-EREKC8m_jkfMEKiBrkNqwSTQCDTPgXbR6I5qM2SgvnedDkFnH3uqXYZEc9Jj5lL0GnMMET2OjmoahuR7oCFa6PbIhtMdwv7P3CWPlxcPs-vi9u7qZnZ-Wxgx5bmYsLq2EmrgpXKqVdZxNwUnHQBrHRetaRVnzDBmjWZGOQPcVbqsOJdGKi12yfEqd5HiywCYm-Bx-ZTuIQ7YcCaEnExkzUd6sqImRcQErlkkH3R6H1GzrL35rr1Z1T7yw5_koQ1g__BvzyM4WoE4LP6P-gISUJE9</recordid><startdate>201209</startdate><enddate>201209</enddate><creator>Georgiev-Hristov, Tihomir</creator><creator>García-Arranz, Mariano</creator><creator>García-Gómez, Ignacio</creator><creator>García-Cabezas, Miguel Angel</creator><creator>Trébol, Jacobo</creator><creator>Vega-Clemente, Luz</creator><creator>Díaz-Agero, Prudencio</creator><creator>García-Olmo, Damián</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201209</creationdate><title>Sutures enriched with adipose-derived stem cells decrease the local acute inflammation after tracheal anastomosis in a murine model</title><author>Georgiev-Hristov, Tihomir ; García-Arranz, Mariano ; García-Gómez, Ignacio ; García-Cabezas, Miguel Angel ; Trébol, Jacobo ; Vega-Clemente, Luz ; Díaz-Agero, Prudencio ; García-Olmo, Damián</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c361t-5088d4e8e129f9b9df1f6ef4fee0bf13bcb9100c00dca0c9fce1f7a27114c49a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adipose Tissue</topic><topic>Anastomosis, Surgical - methods</topic><topic>Animals</topic><topic>Bioprosthesis</topic><topic>Disease Models, Animal</topic><topic>Flow Cytometry</topic><topic>Immunohistochemistry</topic><topic>Inflammation - prevention &amp; control</topic><topic>Male</topic><topic>Mesenchymal Stem Cell Transplantation</topic><topic>Postoperative Complications - prevention &amp; control</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Sensitivity and Specificity</topic><topic>Statistics, Nonparametric</topic><topic>Suture Techniques</topic><topic>Sutures</topic><topic>Trachea - pathology</topic><topic>Trachea - surgery</topic><topic>Tracheotomy - methods</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Georgiev-Hristov, Tihomir</creatorcontrib><creatorcontrib>García-Arranz, Mariano</creatorcontrib><creatorcontrib>García-Gómez, Ignacio</creatorcontrib><creatorcontrib>García-Cabezas, Miguel Angel</creatorcontrib><creatorcontrib>Trébol, Jacobo</creatorcontrib><creatorcontrib>Vega-Clemente, Luz</creatorcontrib><creatorcontrib>Díaz-Agero, Prudencio</creatorcontrib><creatorcontrib>García-Olmo, Damián</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of cardio-thoracic surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Georgiev-Hristov, Tihomir</au><au>García-Arranz, Mariano</au><au>García-Gómez, Ignacio</au><au>García-Cabezas, Miguel Angel</au><au>Trébol, Jacobo</au><au>Vega-Clemente, Luz</au><au>Díaz-Agero, Prudencio</au><au>García-Olmo, Damián</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sutures enriched with adipose-derived stem cells decrease the local acute inflammation after tracheal anastomosis in a murine model</atitle><jtitle>European journal of cardio-thoracic surgery</jtitle><addtitle>Eur J Cardiothorac Surg</addtitle><date>2012-09</date><risdate>2012</risdate><volume>42</volume><issue>3</issue><spage>e40</spage><epage>e47</epage><pages>e40-e47</pages><issn>1010-7940</issn><eissn>1873-734X</eissn><abstract>OBJECTIVES Local inflammatory reaction and tension are the main causes of postoperative complications after tracheal surgery. Adipose-derived stem cells (ASCs) are known to have immunomodulatory activity. The exact mechanism of this activity is not known, although it is possible that they modulate the function of different cells involved in the immune response. Little is known of their impact on acute inflammation, especially in the problematic tracheal area. We aimed to study the effect of ASCs applied locally in an animal model of tracheal resection and anastomosis. METHODS ASCs from the subcutaneous fat of BDIX rats were infected for expression of the enhanced green fluorescent protein (eGFP) and were cultured with Polyglactin 910 sutures to obtain biosutures (ASC-coated sutures). After tracheal resection, 90 BDIX rats (syngeneic, autologous model) underwent anastomosis with biosutures (1.5 × 106 cells/biosuture [Group 1] or 0.5 × 106 cells/biosuture [Group 2]) or conventional sutures (Group 3). The animals were killed after 1, 4, 10, 30 or 60 days and histological and immunofluorescence studies were performed on the anastomotic areas. Inflammatory cell densities were graded semiquantitatively by the pathologist in a blinded fashion. RESULTS In the early period (1 and 4 days), the biosuture groups presented an atypical pattern of acute inflammation, characterized by the almost complete absence of neutrophils, and the presence of abundant lymphocytes and plasma cells, compared with the control group (P &lt; 0.05). Moreover, abundant macrophages/monocytes were immunolocated around blood vessels near the biosutures and between biosuture threads 1 day after anastomosis, whereas the presence of macrophages/monocytes in animals treated with conventional sutures was discrete (P &lt; 0.05). No differences were observed in the later period. No side effects in the biosuture groups were found. CONCLUSIONS Biosutures are a comfortable way of stem cell delivery to the surgical field without modification of the operative protocol. ASCs suppress the local acute inflammatory reaction (increased macrophage migration and decreased neutrophil infiltration) in the tracheal anastomosis and cause an early switch from acute to chronic inflammation.</abstract><cop>Germany</cop><pub>Oxford University Press</pub><pmid>22689184</pmid><doi>10.1093/ejcts/ezs357</doi><oa>free_for_read</oa></addata></record>
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source Oxford University Press Journals All Titles (1996-Current); MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection
subjects Adipose Tissue
Anastomosis, Surgical - methods
Animals
Bioprosthesis
Disease Models, Animal
Flow Cytometry
Immunohistochemistry
Inflammation - prevention & control
Male
Mesenchymal Stem Cell Transplantation
Postoperative Complications - prevention & control
Random Allocation
Rats
Rats, Inbred Strains
Sensitivity and Specificity
Statistics, Nonparametric
Suture Techniques
Sutures
Trachea - pathology
Trachea - surgery
Tracheotomy - methods
Treatment Outcome
title Sutures enriched with adipose-derived stem cells decrease the local acute inflammation after tracheal anastomosis in a murine model
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