Organ preservation with targeted rapamycin nanoparticles: a pre-treatment strategy preventing chronic rejection in vivo.
Identifieur interne : 000533 ( Main/Exploration ); précédent : 000532; suivant : 000534Organ preservation with targeted rapamycin nanoparticles: a pre-treatment strategy preventing chronic rejection in vivo.
Auteurs : Peng Zhu [États-Unis, République populaire de Chine] ; Carl Atkinson [États-Unis] ; Suraj Dixit [États-Unis] ; Qi Cheng [États-Unis, République populaire de Chine] ; Danh Tran [États-Unis] ; Kunal Patel [États-Unis] ; Yu-Lin Jiang [États-Unis] ; Scott Esckilsen [États-Unis] ; Kayla Miller [États-Unis] ; Grace Bazzle [États-Unis] ; Patterson Allen [États-Unis] ; Alfred Moore [États-Unis] ; Ann-Marie Broome [États-Unis] ; Satish N. Nadig [États-Unis]Source :
- RSC advances [ 2046-2069 ] ; 2018.
Abstract
Hypothermic preservation is the standard of care for storing organs prior to transplantation. Endothelial and epithelial injury associated with hypothermic storage causes downstream graft injury and, as such, the choice of an ideal donor organ preservation solution remains controversial. Cold storage solutions, by design, minimize cellular necrosis and optimize cellular osmotic potential, but do little to assuage immunological cell activation or immune cell priming post transplantation. Thus, here we explore the efficacy of our previously described novel Targeted Rapamycin Micelles (TRaM) as an additive to standard-of-care University of Wisconsin preservation solution as a means to alter the immunological microenvironment post transplantation using in vivo models of tracheal and aortic allograft transplantation. In all models of transplantation, grafts pre-treated with 100 ng mL-1 of TRaM augmented preservation solution ex vivo showed a significant inhibition of chronic rejection post-transplantation, as compared to UW augmented with free rapamycin at a ten-fold higher dose. Here, for the first time, we present a novel method of organ pretreatment using a nanotherapeutic-based cellular targeted delivery system that enables donor administration of rapamycin, at a ten-fold decreased dose during cold storage. Clinically, these pretreatment strategies may positively impact post-transplant outcomes and can be readily translated to clinical scenarios.
DOI: 10.1039/c8ra01555d
PubMed: 30220998
PubMed Central: PMC6124302
Affiliations:
- République populaire de Chine, États-Unis
- Caroline du Sud, Hubei
- Columbia (Caroline du Sud), Wuhan
- Université de Caroline du Sud
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Email: broomea@musc.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation></author><author><name sortKey="Bazzle, Grace" sort="Bazzle, Grace" uniqKey="Bazzle G" first="Grace" last="Bazzle">Grace Bazzle</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation></author><author><name sortKey="Allen, Patterson" sort="Allen, Patterson" uniqKey="Allen P" first="Patterson" last="Allen">Patterson Allen</name><affiliation wicri:level="4"><nlm:affiliation>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, USA. Email: nadigsn@musc.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation></author><author><name sortKey="Moore, Alfred" sort="Moore, Alfred" uniqKey="Moore A" first="Alfred" last="Moore">Alfred Moore</name><affiliation wicri:level="4"><nlm:affiliation>Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, USA. Email: broomea@musc.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation></author><author><name sortKey="Broome, Ann Marie" sort="Broome, Ann Marie" uniqKey="Broome A" first="Ann-Marie" last="Broome">Ann-Marie Broome</name><affiliation wicri:level="4"><nlm:affiliation>Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, USA. Email: broomea@musc.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Bioengineering, Clemson University, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Bioengineering, Clemson University</wicri:regionArea><wicri:noRegion>Clemson University</wicri:noRegion></affiliation></author><author><name sortKey="Nadig, Satish N" sort="Nadig, Satish N" uniqKey="Nadig S" first="Satish N" last="Nadig">Satish N. Nadig</name><affiliation wicri:level="4"><nlm:affiliation>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, USA. Email: nadigsn@musc.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2018">2018</date><idno type="RBID">pubmed:30220998</idno><idno type="pmid">30220998</idno><idno type="doi">10.1039/c8ra01555d</idno><idno type="pmc">PMC6124302</idno><idno type="wicri:Area/Main/Corpus">000455</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000455</idno><idno type="wicri:Area/Main/Curation">000455</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000455</idno><idno type="wicri:Area/Main/Exploration">000455</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Organ preservation with targeted rapamycin nanoparticles: a pre-treatment strategy preventing chronic rejection <i>in vivo</i>.</title><author><name sortKey="Zhu, Peng" sort="Zhu, Peng" uniqKey="Zhu P" first="Peng" last="Zhu">Peng Zhu</name><affiliation wicri:level="4"><nlm:affiliation>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, USA. Email: nadigsn@musc.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Institute of Organ Transplantation, Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Organ Transplantation, Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan</wicri:regionArea><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName></affiliation></author><author><name sortKey="Atkinson, Carl" sort="Atkinson, Carl" uniqKey="Atkinson C" first="Carl" last="Atkinson">Carl Atkinson</name><affiliation wicri:level="4"><nlm:affiliation>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, USA. Email: nadigsn@musc.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation></author><author><name sortKey="Dixit, Suraj" sort="Dixit, Suraj" uniqKey="Dixit S" first="Suraj" last="Dixit">Suraj Dixit</name><affiliation wicri:level="4"><nlm:affiliation>Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, USA. Email: broomea@musc.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation></author><author><name sortKey="Cheng, Qi" sort="Cheng, Qi" uniqKey="Cheng Q" first="Qi" last="Cheng">Qi Cheng</name><affiliation wicri:level="4"><nlm:affiliation>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, USA. Email: nadigsn@musc.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Institute of Organ Transplantation, Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Organ Transplantation, Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan</wicri:regionArea><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName></affiliation></author><author><name sortKey="Tran, Danh" sort="Tran, Danh" uniqKey="Tran D" first="Danh" last="Tran">Danh Tran</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation></author><author><name sortKey="Patel, Kunal" sort="Patel, Kunal" uniqKey="Patel K" first="Kunal" last="Patel">Kunal Patel</name><affiliation wicri:level="4"><nlm:affiliation>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, USA. Email: nadigsn@musc.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation></author><author><name sortKey="Jiang, Yu Lin" sort="Jiang, Yu Lin" uniqKey="Jiang Y" first="Yu-Lin" last="Jiang">Yu-Lin Jiang</name><affiliation wicri:level="4"><nlm:affiliation>Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, USA. Email: broomea@musc.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation></author><author><name sortKey="Esckilsen, Scott" sort="Esckilsen, Scott" uniqKey="Esckilsen S" first="Scott" last="Esckilsen">Scott Esckilsen</name><affiliation wicri:level="4"><nlm:affiliation>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, USA. Email: nadigsn@musc.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation></author><author><name sortKey="Miller, Kayla" sort="Miller, Kayla" uniqKey="Miller K" first="Kayla" last="Miller">Kayla Miller</name><affiliation wicri:level="4"><nlm:affiliation>Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, USA. Email: broomea@musc.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation></author><author><name sortKey="Bazzle, Grace" sort="Bazzle, Grace" uniqKey="Bazzle G" first="Grace" last="Bazzle">Grace Bazzle</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation></author><author><name sortKey="Allen, Patterson" sort="Allen, Patterson" uniqKey="Allen P" first="Patterson" last="Allen">Patterson Allen</name><affiliation wicri:level="4"><nlm:affiliation>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, USA. Email: nadigsn@musc.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation></author><author><name sortKey="Moore, Alfred" sort="Moore, Alfred" uniqKey="Moore A" first="Alfred" last="Moore">Alfred Moore</name><affiliation wicri:level="4"><nlm:affiliation>Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, USA. Email: broomea@musc.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation></author><author><name sortKey="Broome, Ann Marie" sort="Broome, Ann Marie" uniqKey="Broome A" first="Ann-Marie" last="Broome">Ann-Marie Broome</name><affiliation wicri:level="4"><nlm:affiliation>Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, USA. Email: broomea@musc.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Bioengineering, Clemson University, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Bioengineering, Clemson University</wicri:regionArea><wicri:noRegion>Clemson University</wicri:noRegion></affiliation></author><author><name sortKey="Nadig, Satish N" sort="Nadig, Satish N" uniqKey="Nadig S" first="Satish N" last="Nadig">Satish N. Nadig</name><affiliation wicri:level="4"><nlm:affiliation>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, USA. Email: nadigsn@musc.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina</wicri:regionArea><placeName><settlement type="city">Columbia (Caroline du Sud)</settlement><region type="state">Caroline du Sud</region></placeName><orgName type="university">Université de Caroline du Sud</orgName></affiliation></author></analytic><series><title level="j">RSC advances</title><idno type="ISSN">2046-2069</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Hypothermic preservation is the standard of care for storing organs prior to transplantation. Endothelial and epithelial injury associated with hypothermic storage causes downstream graft injury and, as such, the choice of an ideal donor organ preservation solution remains controversial. Cold storage solutions, by design, minimize cellular necrosis and optimize cellular osmotic potential, but do little to assuage immunological cell activation or immune cell priming post transplantation. Thus, here we explore the efficacy of our previously described novel Targeted Rapamycin Micelles (TRaM) as an additive to standard-of-care University of Wisconsin preservation solution as a means to alter the immunological microenvironment post transplantation using <i>in vivo</i> models of tracheal and aortic allograft transplantation. In all models of transplantation, grafts pre-treated with 100 ng mL<sup>-1</sup> of TRaM augmented preservation solution <i>ex vivo</i> showed a significant inhibition of chronic rejection post-transplantation, as compared to UW augmented with free rapamycin at a ten-fold higher dose. Here, for the first time, we present a novel method of organ pretreatment using a nanotherapeutic-based cellular targeted delivery system that enables donor administration of rapamycin, at a ten-fold decreased dose during cold storage. Clinically, these pretreatment strategies may positively impact post-transplant outcomes and can be readily translated to clinical scenarios.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">30220998</PMID><DateRevised><Year>2020</Year><Month>09</Month><Day>28</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">2046-2069</ISSN><JournalIssue CitedMedium="Print"><Volume>8</Volume><Issue>46</Issue><PubDate><Year>2018</Year><Month>Jul</Month><Day>23</Day></PubDate></JournalIssue><Title>RSC advances</Title><ISOAbbreviation>RSC Adv</ISOAbbreviation></Journal><ArticleTitle>Organ preservation with targeted rapamycin nanoparticles: a pre-treatment strategy preventing chronic rejection <i>in vivo</i>.</ArticleTitle><Pagination><MedlinePgn>25909-25919</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1039/c8ra01555d</ELocationID><Abstract><AbstractText>Hypothermic preservation is the standard of care for storing organs prior to transplantation. Endothelial and epithelial injury associated with hypothermic storage causes downstream graft injury and, as such, the choice of an ideal donor organ preservation solution remains controversial. Cold storage solutions, by design, minimize cellular necrosis and optimize cellular osmotic potential, but do little to assuage immunological cell activation or immune cell priming post transplantation. Thus, here we explore the efficacy of our previously described novel Targeted Rapamycin Micelles (TRaM) as an additive to standard-of-care University of Wisconsin preservation solution as a means to alter the immunological microenvironment post transplantation using <i>in vivo</i> models of tracheal and aortic allograft transplantation. In all models of transplantation, grafts pre-treated with 100 ng mL<sup>-1</sup> of TRaM augmented preservation solution <i>ex vivo</i> showed a significant inhibition of chronic rejection post-transplantation, as compared to UW augmented with free rapamycin at a ten-fold higher dose. Here, for the first time, we present a novel method of organ pretreatment using a nanotherapeutic-based cellular targeted delivery system that enables donor administration of rapamycin, at a ten-fold decreased dose during cold storage. Clinically, these pretreatment strategies may positively impact post-transplant outcomes and can be readily translated to clinical scenarios.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zhu</LastName><ForeName>Peng</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, USA. Email: nadigsn@musc.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Organ Transplantation, Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Atkinson</LastName><ForeName>Carl</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, USA. Email: nadigsn@musc.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dixit</LastName><ForeName>Suraj</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, USA. Email: broomea@musc.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cheng</LastName><ForeName>Qi</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, USA. Email: nadigsn@musc.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Organ Transplantation, Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tran</LastName><ForeName>Danh</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Patel</LastName><ForeName>Kunal</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, USA. Email: nadigsn@musc.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jiang</LastName><ForeName>Yu-Lin</ForeName><Initials>YL</Initials><AffiliationInfo><Affiliation>Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, USA. Email: broomea@musc.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Esckilsen</LastName><ForeName>Scott</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, USA. Email: nadigsn@musc.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Miller</LastName><ForeName>Kayla</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, USA. Email: broomea@musc.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bazzle</LastName><ForeName>Grace</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Allen</LastName><ForeName>Patterson</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, USA. Email: nadigsn@musc.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moore</LastName><ForeName>Alfred</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, USA. Email: broomea@musc.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Broome</LastName><ForeName>Ann-Marie</ForeName><Initials>AM</Initials><Identifier Source="ORCID">0000-0002-2384-5212</Identifier><AffiliationInfo><Affiliation>Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, USA. Email: broomea@musc.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Bioengineering, Clemson University, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nadig</LastName><ForeName>Satish N</ForeName><Initials>SN</Initials><AffiliationInfo><Affiliation>Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, USA. Email: nadigsn@musc.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>K08 EB019495</GrantID><Acronym>EB</Acronym><Agency>NIBIB NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>RSC Adv</MedlineTA><NlmUniqueID>101581657</NlmUniqueID><ISSNLinking>2046-2069</ISSNLinking></MedlineJournalInfo></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>02</Month><Day>21</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2018</Year><Month>06</Month><Day>24</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>9</Month><Day>18</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>9</Month><Day>18</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2018</Year><Month>9</Month><Day>18</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30220998</ArticleId><ArticleId IdType="doi">10.1039/c8ra01555d</ArticleId><ArticleId IdType="pii">c8ra01555d</ArticleId><ArticleId IdType="pmc">PMC6124302</ArticleId></ArticleIdList><pmc-dir>pmcsd</pmc-dir>
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Carl" sort="Atkinson, Carl" uniqKey="Atkinson C" first="Carl" last="Atkinson">Carl Atkinson</name><name sortKey="Atkinson, Carl" sort="Atkinson, Carl" uniqKey="Atkinson C" first="Carl" last="Atkinson">Carl Atkinson</name><name sortKey="Bazzle, Grace" sort="Bazzle, Grace" uniqKey="Bazzle G" first="Grace" last="Bazzle">Grace Bazzle</name><name sortKey="Broome, Ann Marie" sort="Broome, Ann Marie" uniqKey="Broome A" first="Ann-Marie" last="Broome">Ann-Marie Broome</name><name sortKey="Broome, Ann Marie" sort="Broome, Ann Marie" uniqKey="Broome A" first="Ann-Marie" last="Broome">Ann-Marie Broome</name><name sortKey="Cheng, Qi" sort="Cheng, Qi" uniqKey="Cheng Q" first="Qi" last="Cheng">Qi Cheng</name><name sortKey="Cheng, Qi" sort="Cheng, Qi" uniqKey="Cheng Q" first="Qi" last="Cheng">Qi Cheng</name><name sortKey="Dixit, Suraj" sort="Dixit, Suraj" uniqKey="Dixit S" first="Suraj" last="Dixit">Suraj Dixit</name><name sortKey="Esckilsen, Scott" sort="Esckilsen, Scott" uniqKey="Esckilsen S" first="Scott" last="Esckilsen">Scott Esckilsen</name><name sortKey="Esckilsen, Scott" sort="Esckilsen, Scott" uniqKey="Esckilsen S" first="Scott" last="Esckilsen">Scott Esckilsen</name><name sortKey="Jiang, Yu Lin" sort="Jiang, Yu Lin" uniqKey="Jiang Y" first="Yu-Lin" last="Jiang">Yu-Lin Jiang</name><name sortKey="Miller, Kayla" sort="Miller, Kayla" uniqKey="Miller K" first="Kayla" last="Miller">Kayla Miller</name><name sortKey="Moore, Alfred" sort="Moore, Alfred" uniqKey="Moore A" first="Alfred" last="Moore">Alfred Moore</name><name sortKey="Nadig, Satish N" sort="Nadig, Satish N" uniqKey="Nadig S" first="Satish N" last="Nadig">Satish N. Nadig</name><name sortKey="Nadig, Satish N" sort="Nadig, Satish N" uniqKey="Nadig S" first="Satish N" last="Nadig">Satish N. Nadig</name><name sortKey="Patel, Kunal" sort="Patel, Kunal" uniqKey="Patel K" first="Kunal" last="Patel">Kunal Patel</name><name sortKey="Patel, Kunal" sort="Patel, Kunal" uniqKey="Patel K" first="Kunal" last="Patel">Kunal Patel</name><name sortKey="Tran, Danh" sort="Tran, Danh" uniqKey="Tran D" first="Danh" last="Tran">Danh Tran</name><name sortKey="Zhu, Peng" sort="Zhu, Peng" uniqKey="Zhu P" first="Peng" last="Zhu">Peng Zhu</name></country><country name="République populaire de Chine"><region name="Hubei"><name sortKey="Zhu, Peng" sort="Zhu, Peng" uniqKey="Zhu P" first="Peng" last="Zhu">Peng Zhu</name></region><name sortKey="Cheng, Qi" sort="Cheng, Qi" uniqKey="Cheng Q" first="Qi" last="Cheng">Qi Cheng</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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