Successful immunosuppressant-free heterotopic transplantation of tracheal allografts in the pig
Abstract OBJECTIVES: It has been demonstrated that both heterotopic and orthotopic transplants of epithelium-denuded cryopreserved tracheal allografts are feasible in immunosuppressant-free rabbits. Validation of these results in large animals is required before considering clinical applications. We...
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Veröffentlicht in: | European journal of cardio-thoracic surgery 2017-08, Vol.52 (2), p.248-255 |
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creator | De Wolf, Julien Brieu, Mathias Zawadzki, Christophe Ung, Alexandre Kipnis, Eric Jashari, Ramadan Hubert, Thomas Fayoux, Pierre Mariette, Christophe Copin, Marie-Christine Wurtz, Alain |
description | Abstract
OBJECTIVES: It has been demonstrated that both heterotopic and orthotopic transplants of epithelium-denuded cryopreserved tracheal allografts are feasible in immunosuppressant-free rabbits. Validation of these results in large animals is required before considering clinical applications. We evaluated the viability, immune tolerance and strain properties of such tracheal allografts heterotopically transplanted in a pig model.
METHODS: Ten tracheal segments, 5 short (5 rings) and 5 long (10 rings), were obtained from male Landrace pigs. The tracheal segments were surgically denuded of their epithelium, then cryopreserved and stored in a tissue bank for 33 to 232 days. After thawing, tracheal segments stented with a silicone tube were wrapped in the omentum in 2 groups of 5 female recipients. The animals did not receive any immunosuppressive drugs. The animals were euthanized from Day 6 to Day 90 in both groups.
RESULTS: An effective revascularization of allografts regardless of length was observed. Lymphocyte infiltrate was shown in the early postoperative period and became non-significant after 30 days. Allografts displayed high levels of neoangiogenesis and viable cartilage rings with islets of calcification. Biomechanical measurements demonstrated strain properties similar to those of a fresh tracheal segment from Day 58.
CONCLUSIONS: Our results demonstrate the acceptability and satisfactory stiffness of epithelium-denuded cryopreserved tracheal allografts implanted in the omentum, despite the absence of immunosuppressive drugs. Since the omentum has the capability to reach the tracheal region, this approach should be investigated in the setting of orthotopic transplants in a pig model before considering clinical applications. |
doi_str_mv | 10.1093/ejcts/ezx116 |
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OBJECTIVES: It has been demonstrated that both heterotopic and orthotopic transplants of epithelium-denuded cryopreserved tracheal allografts are feasible in immunosuppressant-free rabbits. Validation of these results in large animals is required before considering clinical applications. We evaluated the viability, immune tolerance and strain properties of such tracheal allografts heterotopically transplanted in a pig model.
METHODS: Ten tracheal segments, 5 short (5 rings) and 5 long (10 rings), were obtained from male Landrace pigs. The tracheal segments were surgically denuded of their epithelium, then cryopreserved and stored in a tissue bank for 33 to 232 days. After thawing, tracheal segments stented with a silicone tube were wrapped in the omentum in 2 groups of 5 female recipients. The animals did not receive any immunosuppressive drugs. The animals were euthanized from Day 6 to Day 90 in both groups.
RESULTS: An effective revascularization of allografts regardless of length was observed. Lymphocyte infiltrate was shown in the early postoperative period and became non-significant after 30 days. Allografts displayed high levels of neoangiogenesis and viable cartilage rings with islets of calcification. Biomechanical measurements demonstrated strain properties similar to those of a fresh tracheal segment from Day 58.
CONCLUSIONS: Our results demonstrate the acceptability and satisfactory stiffness of epithelium-denuded cryopreserved tracheal allografts implanted in the omentum, despite the absence of immunosuppressive drugs. Since the omentum has the capability to reach the tracheal region, this approach should be investigated in the setting of orthotopic transplants in a pig model before considering clinical applications.</description><identifier>ISSN: 1010-7940</identifier><identifier>ISSN: 1567-4258</identifier><identifier>EISSN: 1873-734X</identifier><identifier>DOI: 10.1093/ejcts/ezx116</identifier><identifier>PMID: 28472471</identifier><language>eng</language><publisher>Germany: Oxford University Press</publisher><subject>Allografts - physiology ; Allografts - surgery ; Allografts - transplantation ; Animals ; Bioengineering ; Biomaterials ; Cryopreservation ; Female ; Immune Tolerance ; Life Sciences ; Male ; Omentum - physiology ; Omentum - surgery ; Omentum - transplantation ; Swine ; Tissue Survival - physiology ; Trachea - physiology ; Trachea - surgery ; Trachea - transplantation ; Transplantation, Heterotopic</subject><ispartof>European journal of cardio-thoracic surgery, 2017-08, Vol.52 (2), p.248-255</ispartof><rights>The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. 2017</rights><rights>The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c395t-729e8afc09b4ec700a1bde2ac716b93717025947ac50094e414b32283c86d7ff3</citedby><cites>FETCH-LOGICAL-c395t-729e8afc09b4ec700a1bde2ac716b93717025947ac50094e414b32283c86d7ff3</cites><orcidid>0000-0002-3566-3758 ; 0000-0003-0190-3538 ; 0000-0002-4729-7054</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,881,1578,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28472471$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01631592$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>De Wolf, Julien</creatorcontrib><creatorcontrib>Brieu, Mathias</creatorcontrib><creatorcontrib>Zawadzki, Christophe</creatorcontrib><creatorcontrib>Ung, Alexandre</creatorcontrib><creatorcontrib>Kipnis, Eric</creatorcontrib><creatorcontrib>Jashari, Ramadan</creatorcontrib><creatorcontrib>Hubert, Thomas</creatorcontrib><creatorcontrib>Fayoux, Pierre</creatorcontrib><creatorcontrib>Mariette, Christophe</creatorcontrib><creatorcontrib>Copin, Marie-Christine</creatorcontrib><creatorcontrib>Wurtz, Alain</creatorcontrib><title>Successful immunosuppressant-free heterotopic transplantation of tracheal allografts in the pig</title><title>European journal of cardio-thoracic surgery</title><addtitle>Eur J Cardiothorac Surg</addtitle><description>Abstract
OBJECTIVES: It has been demonstrated that both heterotopic and orthotopic transplants of epithelium-denuded cryopreserved tracheal allografts are feasible in immunosuppressant-free rabbits. Validation of these results in large animals is required before considering clinical applications. We evaluated the viability, immune tolerance and strain properties of such tracheal allografts heterotopically transplanted in a pig model.
METHODS: Ten tracheal segments, 5 short (5 rings) and 5 long (10 rings), were obtained from male Landrace pigs. The tracheal segments were surgically denuded of their epithelium, then cryopreserved and stored in a tissue bank for 33 to 232 days. After thawing, tracheal segments stented with a silicone tube were wrapped in the omentum in 2 groups of 5 female recipients. The animals did not receive any immunosuppressive drugs. The animals were euthanized from Day 6 to Day 90 in both groups.
RESULTS: An effective revascularization of allografts regardless of length was observed. Lymphocyte infiltrate was shown in the early postoperative period and became non-significant after 30 days. Allografts displayed high levels of neoangiogenesis and viable cartilage rings with islets of calcification. Biomechanical measurements demonstrated strain properties similar to those of a fresh tracheal segment from Day 58.
CONCLUSIONS: Our results demonstrate the acceptability and satisfactory stiffness of epithelium-denuded cryopreserved tracheal allografts implanted in the omentum, despite the absence of immunosuppressive drugs. Since the omentum has the capability to reach the tracheal region, this approach should be investigated in the setting of orthotopic transplants in a pig model before considering clinical applications.</description><subject>Allografts - physiology</subject><subject>Allografts - surgery</subject><subject>Allografts - transplantation</subject><subject>Animals</subject><subject>Bioengineering</subject><subject>Biomaterials</subject><subject>Cryopreservation</subject><subject>Female</subject><subject>Immune Tolerance</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Omentum - physiology</subject><subject>Omentum - surgery</subject><subject>Omentum - transplantation</subject><subject>Swine</subject><subject>Tissue Survival - physiology</subject><subject>Trachea - physiology</subject><subject>Trachea - surgery</subject><subject>Trachea - transplantation</subject><subject>Transplantation, Heterotopic</subject><issn>1010-7940</issn><issn>1567-4258</issn><issn>1873-734X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1P3DAQhq2qCJaPW89Vbi1SU8YfieMjWkEXaSUOFImb5XjHbFASp7ZTFX49WUL3yGlG7zx6pXkI-ULhJwXFL_DJpniBL_8oLT-RBa0kzyUXD5-nHSjkUgk4IscxPgFAyZk8JEesEpIJSRdE343WYoxubLOm68bex3EYwpSYPuUuIGZbTBh88kNjsxRMH4d2upnU-D7zbhfZLZo2M23rH4NxKWZNn6UtZkPzeEoOnGkjnr3PE3J_ffV7ucrXt79ulpfr3HJVpFwyhZVxFlQt0EoAQ-sNMmMlLWvFJZXACiWksQWAEiioqDljFbdVuZHO8RNyPvduTauH0HQmPGtvGr26XOtdBrTktFDsL53Y7zM7BP9nxJh010SL7fQW-jFqWqkSBCsLmNAfM2qDjzGg23dT0Dv9-k2_nvVP-Nf35rHucLOH__uegG8z4Mfh46pXrsGQ8w</recordid><startdate>20170801</startdate><enddate>20170801</enddate><creator>De Wolf, Julien</creator><creator>Brieu, Mathias</creator><creator>Zawadzki, Christophe</creator><creator>Ung, Alexandre</creator><creator>Kipnis, Eric</creator><creator>Jashari, Ramadan</creator><creator>Hubert, Thomas</creator><creator>Fayoux, Pierre</creator><creator>Mariette, Christophe</creator><creator>Copin, Marie-Christine</creator><creator>Wurtz, Alain</creator><general>Oxford University Press</general><general>Elsevier</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><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-3566-3758</orcidid><orcidid>https://orcid.org/0000-0003-0190-3538</orcidid><orcidid>https://orcid.org/0000-0002-4729-7054</orcidid></search><sort><creationdate>20170801</creationdate><title>Successful immunosuppressant-free heterotopic transplantation of tracheal allografts in the pig</title><author>De Wolf, Julien ; Brieu, Mathias ; Zawadzki, Christophe ; Ung, Alexandre ; Kipnis, Eric ; Jashari, Ramadan ; Hubert, Thomas ; Fayoux, Pierre ; Mariette, Christophe ; Copin, Marie-Christine ; Wurtz, Alain</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c395t-729e8afc09b4ec700a1bde2ac716b93717025947ac50094e414b32283c86d7ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Allografts - physiology</topic><topic>Allografts - surgery</topic><topic>Allografts - transplantation</topic><topic>Animals</topic><topic>Bioengineering</topic><topic>Biomaterials</topic><topic>Cryopreservation</topic><topic>Female</topic><topic>Immune Tolerance</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Omentum - physiology</topic><topic>Omentum - surgery</topic><topic>Omentum - transplantation</topic><topic>Swine</topic><topic>Tissue Survival - physiology</topic><topic>Trachea - physiology</topic><topic>Trachea - surgery</topic><topic>Trachea - transplantation</topic><topic>Transplantation, Heterotopic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>De Wolf, Julien</creatorcontrib><creatorcontrib>Brieu, Mathias</creatorcontrib><creatorcontrib>Zawadzki, Christophe</creatorcontrib><creatorcontrib>Ung, Alexandre</creatorcontrib><creatorcontrib>Kipnis, Eric</creatorcontrib><creatorcontrib>Jashari, Ramadan</creatorcontrib><creatorcontrib>Hubert, Thomas</creatorcontrib><creatorcontrib>Fayoux, Pierre</creatorcontrib><creatorcontrib>Mariette, Christophe</creatorcontrib><creatorcontrib>Copin, Marie-Christine</creatorcontrib><creatorcontrib>Wurtz, Alain</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><collection>Hyper Article en Ligne (HAL)</collection><jtitle>European journal of cardio-thoracic surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>De Wolf, Julien</au><au>Brieu, Mathias</au><au>Zawadzki, Christophe</au><au>Ung, Alexandre</au><au>Kipnis, Eric</au><au>Jashari, Ramadan</au><au>Hubert, Thomas</au><au>Fayoux, Pierre</au><au>Mariette, Christophe</au><au>Copin, Marie-Christine</au><au>Wurtz, Alain</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Successful immunosuppressant-free heterotopic transplantation of tracheal allografts in the pig</atitle><jtitle>European journal of cardio-thoracic surgery</jtitle><addtitle>Eur J Cardiothorac Surg</addtitle><date>2017-08-01</date><risdate>2017</risdate><volume>52</volume><issue>2</issue><spage>248</spage><epage>255</epage><pages>248-255</pages><issn>1010-7940</issn><issn>1567-4258</issn><eissn>1873-734X</eissn><abstract>Abstract
OBJECTIVES: It has been demonstrated that both heterotopic and orthotopic transplants of epithelium-denuded cryopreserved tracheal allografts are feasible in immunosuppressant-free rabbits. Validation of these results in large animals is required before considering clinical applications. We evaluated the viability, immune tolerance and strain properties of such tracheal allografts heterotopically transplanted in a pig model.
METHODS: Ten tracheal segments, 5 short (5 rings) and 5 long (10 rings), were obtained from male Landrace pigs. The tracheal segments were surgically denuded of their epithelium, then cryopreserved and stored in a tissue bank for 33 to 232 days. After thawing, tracheal segments stented with a silicone tube were wrapped in the omentum in 2 groups of 5 female recipients. The animals did not receive any immunosuppressive drugs. The animals were euthanized from Day 6 to Day 90 in both groups.
RESULTS: An effective revascularization of allografts regardless of length was observed. Lymphocyte infiltrate was shown in the early postoperative period and became non-significant after 30 days. Allografts displayed high levels of neoangiogenesis and viable cartilage rings with islets of calcification. Biomechanical measurements demonstrated strain properties similar to those of a fresh tracheal segment from Day 58.
CONCLUSIONS: Our results demonstrate the acceptability and satisfactory stiffness of epithelium-denuded cryopreserved tracheal allografts implanted in the omentum, despite the absence of immunosuppressive drugs. Since the omentum has the capability to reach the tracheal region, this approach should be investigated in the setting of orthotopic transplants in a pig model before considering clinical applications.</abstract><cop>Germany</cop><pub>Oxford University Press</pub><pmid>28472471</pmid><doi>10.1093/ejcts/ezx116</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-3566-3758</orcidid><orcidid>https://orcid.org/0000-0003-0190-3538</orcidid><orcidid>https://orcid.org/0000-0002-4729-7054</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Allografts - physiology Allografts - surgery Allografts - transplantation Animals Bioengineering Biomaterials Cryopreservation Female Immune Tolerance Life Sciences Male Omentum - physiology Omentum - surgery Omentum - transplantation Swine Tissue Survival - physiology Trachea - physiology Trachea - surgery Trachea - transplantation Transplantation, Heterotopic |
title | Successful immunosuppressant-free heterotopic transplantation of tracheal allografts in the pig |
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