RapamycinFungusV1, Main, Exploration, bibRecord, 000296

Localized immune tolerance from FasL-functionalized PLG scaffolds.

Identifieur interne : 000296 ( Main/Exploration ); précédent : 000295; suivant : 000297

Localized immune tolerance from FasL-functionalized PLG scaffolds.

Auteurs : Michael Skoumal [États-Unis] ; Kyle B. Woodward [États-Unis] ; Hong Zhao [États-Unis] ; Feng Wang [États-Unis] ; Esma S. Yolcu [États-Unis] ; Ryan M. Pearson [États-Unis] ; Kevin R. Hughes [États-Unis] ; Andrés J. García [États-Unis] ; Lonnie D. Shea [États-Unis] ; Haval Shirwan [États-Unis]

Source :

Biomaterials [ 1878-5905 ] ; 2019.

RBID : pubmed:30458362

Descripteurs français

English descriptors

KwdEn :
- Animals (MeSH), Fas Ligand Protein (immunology), Graft Survival (MeSH), Immobilized Proteins (immunology), Immune Tolerance (MeSH), Islets of Langerhans (immunology), Islets of Langerhans Transplantation (immunology), Islets of Langerhans Transplantation (methods), Mice, Inbred BALB C (MeSH), Mice, Inbred C57BL (MeSH), Polylactic Acid-Polyglycolic Acid Copolymer (chemistry), Recombinant Proteins (immunology), Streptavidin (immunology), Tissue Scaffolds (chemistry).
MESH :
- chemical , chemistry : Polylactic Acid-Polyglycolic Acid Copolymer.
- chemical , immunology : Fas Ligand Protein, Immobilized Proteins, Recombinant Proteins, Streptavidin.
- chemistry : Tissue Scaffolds.
- immunology : Islets of Langerhans, Islets of Langerhans Transplantation.
- methods : Islets of Langerhans Transplantation.
- Animals, Graft Survival, Immune Tolerance, Mice, Inbred BALB C, Mice, Inbred C57BL.

Abstract

Intraportal allogeneic islet transplantation has been demonstrated as a potential therapy for type 1 diabetes (T1D). The placement of islets into the liver and chronic immunosuppression to control rejection are two major limitations of islet transplantation. We hypothesize that localized immunomodulation with a novel form of FasL chimeric with streptavidin, SA-FasL, can provide protection and long-term function of islets at an extrahepatic site in the absence of chronic immunosuppression. Allogeneic islets modified with biotin and engineered to transiently display SA-FasL on their surface showed sustained survival following transplantation on microporous scaffolds into the peritoneal fat in combination with a short course (15 days) of rapamycin treatment. The challenges with modifying islets for clinical translation motivated the modification of scaffolds with SA-FasL as an off-the-shelf product. Poly (lactide-co-glycolide) (PLG) was conjugated with biotin and fabricated into particles and subsequently formed into microporous scaffolds to allow for rapid and efficient conjugation with SA-FasL. Biotinylated particles and scaffolds efficiently bound SA-FasL and induced apoptosis in cells expressing Fas receptor (FasR). Scaffolds functionalized with SA-FasL were subsequently seeded with allogeneic islets and transplanted into the peritoneal fat under the short-course of rapamycin treatment. Scaffolds modified with SA-FasL had robust engraftment of the transplanted islets that restored normoglycemia for 200 days. Transplantation without rapamycin or without SA-FasL did not support long-term survival and function. This work demonstrates that scaffolds functionalized with SA-FasL support allogeneic islet engraftment and long-term survival and function in an extrahepatic site in the absence of chronic immunosuppression with significant potential for clinical translation.

DOI: 10.1016/j.biomaterials.2018.11.015
PubMed: 30458362
PubMed Central: PMC6331284

Affiliations:

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Le document en format XML

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<series><title level="j">Biomaterials</title>
<idno type="eISSN">1878-5905</idno>
<imprint><date when="2019" type="published">2019</date>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term>
<term>Fas Ligand Protein (immunology)</term>
<term>Graft Survival (MeSH)</term>
<term>Immobilized Proteins (immunology)</term>
<term>Immune Tolerance (MeSH)</term>
<term>Islets of Langerhans (immunology)</term>
<term>Islets of Langerhans Transplantation (immunology)</term>
<term>Islets of Langerhans Transplantation (methods)</term>
<term>Mice, Inbred BALB C (MeSH)</term>
<term>Mice, Inbred C57BL (MeSH)</term>
<term>Polylactic Acid-Polyglycolic Acid Copolymer (chemistry)</term>
<term>Recombinant Proteins (immunology)</term>
<term>Streptavidin (immunology)</term>
<term>Tissue Scaffolds (chemistry)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term>
<term>Copolymère d'acide poly(lactique-co-glycolique) (composition chimique)</term>
<term>Ilots pancréatiques (immunologie)</term>
<term>Ligand de Fas (immunologie)</term>
<term>Protéines immobilisées (immunologie)</term>
<term>Protéines recombinantes (immunologie)</term>
<term>Souris de lignée BALB C (MeSH)</term>
<term>Souris de lignée C57BL (MeSH)</term>
<term>Streptavidine (immunologie)</term>
<term>Structures d'échafaudage tissulaires (composition chimique)</term>
<term>Survie du greffon (MeSH)</term>
<term>Tolérance immunitaire (MeSH)</term>
<term>Transplantation d'ilots de Langerhans (immunologie)</term>
<term>Transplantation d'ilots de Langerhans (méthodes)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Polylactic Acid-Polyglycolic Acid Copolymer</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Fas Ligand Protein</term>
<term>Immobilized Proteins</term>
<term>Recombinant Proteins</term>
<term>Streptavidin</term>
</keywords>
<keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Tissue Scaffolds</term>
</keywords>
<keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr"><term>Copolymère d'acide poly(lactique-co-glycolique)</term>
<term>Structures d'échafaudage tissulaires</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Ilots pancréatiques</term>
<term>Ligand de Fas</term>
<term>Protéines immobilisées</term>
<term>Protéines recombinantes</term>
<term>Streptavidine</term>
<term>Transplantation d'ilots de Langerhans</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Islets of Langerhans</term>
<term>Islets of Langerhans Transplantation</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Islets of Langerhans Transplantation</term>
</keywords>
<keywords scheme="MESH" qualifier="méthodes" xml:lang="fr"><term>Transplantation d'ilots de Langerhans</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Graft Survival</term>
<term>Immune Tolerance</term>
<term>Mice, Inbred BALB C</term>
<term>Mice, Inbred C57BL</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Souris de lignée BALB C</term>
<term>Souris de lignée C57BL</term>
<term>Survie du greffon</term>
<term>Tolérance immunitaire</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Intraportal allogeneic islet transplantation has been demonstrated as a potential therapy for type 1 diabetes (T1D). The placement of islets into the liver and chronic immunosuppression to control rejection are two major limitations of islet transplantation. We hypothesize that localized immunomodulation with a novel form of FasL chimeric with streptavidin, SA-FasL, can provide protection and long-term function of islets at an extrahepatic site in the absence of chronic immunosuppression. Allogeneic islets modified with biotin and engineered to transiently display SA-FasL on their surface showed sustained survival following transplantation on microporous scaffolds into the peritoneal fat in combination with a short course (15 days) of rapamycin treatment. The challenges with modifying islets for clinical translation motivated the modification of scaffolds with SA-FasL as an off-the-shelf product. Poly (lactide-co-glycolide) (PLG) was conjugated with biotin and fabricated into particles and subsequently formed into microporous scaffolds to allow for rapid and efficient conjugation with SA-FasL. Biotinylated particles and scaffolds efficiently bound SA-FasL and induced apoptosis in cells expressing Fas receptor (FasR). Scaffolds functionalized with SA-FasL were subsequently seeded with allogeneic islets and transplanted into the peritoneal fat under the short-course of rapamycin treatment. Scaffolds modified with SA-FasL had robust engraftment of the transplanted islets that restored normoglycemia for 200 days. Transplantation without rapamycin or without SA-FasL did not support long-term survival and function. This work demonstrates that scaffolds functionalized with SA-FasL support allogeneic islet engraftment and long-term survival and function in an extrahepatic site in the absence of chronic immunosuppression with significant potential for clinical translation.</div>
</front>
</TEI>
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<DateCompleted><Year>2020</Year>
<Month>03</Month>
<Day>11</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>03</Month>
<Day>11</Day>
</DateRevised>
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<JournalIssue CitedMedium="Internet"><Volume>192</Volume>
<PubDate><Year>2019</Year>
<Month>02</Month>
</PubDate>
</JournalIssue>
<Title>Biomaterials</Title>
<ISOAbbreviation>Biomaterials</ISOAbbreviation>
</Journal>
<ArticleTitle>Localized immune tolerance from FasL-functionalized PLG scaffolds.</ArticleTitle>
<Pagination><MedlinePgn>271-281</MedlinePgn>
</Pagination>
<ELocationID EIdType="pii" ValidYN="Y">S0142-9612(18)30792-0</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.biomaterials.2018.11.015</ELocationID>
<Abstract><AbstractText>Intraportal allogeneic islet transplantation has been demonstrated as a potential therapy for type 1 diabetes (T1D). The placement of islets into the liver and chronic immunosuppression to control rejection are two major limitations of islet transplantation. We hypothesize that localized immunomodulation with a novel form of FasL chimeric with streptavidin, SA-FasL, can provide protection and long-term function of islets at an extrahepatic site in the absence of chronic immunosuppression. Allogeneic islets modified with biotin and engineered to transiently display SA-FasL on their surface showed sustained survival following transplantation on microporous scaffolds into the peritoneal fat in combination with a short course (15 days) of rapamycin treatment. The challenges with modifying islets for clinical translation motivated the modification of scaffolds with SA-FasL as an off-the-shelf product. Poly (lactide-co-glycolide) (PLG) was conjugated with biotin and fabricated into particles and subsequently formed into microporous scaffolds to allow for rapid and efficient conjugation with SA-FasL. Biotinylated particles and scaffolds efficiently bound SA-FasL and induced apoptosis in cells expressing Fas receptor (FasR). Scaffolds functionalized with SA-FasL were subsequently seeded with allogeneic islets and transplanted into the peritoneal fat under the short-course of rapamycin treatment. Scaffolds modified with SA-FasL had robust engraftment of the transplanted islets that restored normoglycemia for 200 days. Transplantation without rapamycin or without SA-FasL did not support long-term survival and function. This work demonstrates that scaffolds functionalized with SA-FasL support allogeneic islet engraftment and long-term survival and function in an extrahepatic site in the absence of chronic immunosuppression with significant potential for clinical translation.</AbstractText>
<CopyrightInformation>Copyright © 2018 Elsevier Ltd. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Skoumal</LastName>
<ForeName>Michael</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Woodward</LastName>
<ForeName>Kyle B</ForeName>
<Initials>KB</Initials>
<AffiliationInfo><Affiliation>Institute of Cellular Therapeutics, Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhao</LastName>
<ForeName>Hong</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Institute of Cellular Therapeutics, Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wang</LastName>
<ForeName>Feng</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Institute of Cellular Therapeutics, Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, USA.</Affiliation>
</AffiliationInfo>
</Author>
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	Serveur d'exploration sur la rapamycine et les champignons
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Serveur d'exploration sur la rapamycine et les champignons

Localized immune tolerance from FasL-functionalized PLG scaffolds.

Localized immune tolerance from FasL-functionalized PLG scaffolds.

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