RGD-containing elastin-like polypeptide improves islet transplantation outcomes in diabetic mice
[Display omitted] Successful islet transplantation critically depends on the isolation of healthy islets. However, the islet isolation procedure itself contributes to islet death due to the destruction of intra- and peri-islet extracellular matrices (ECMs) during digestion. We investigated whether a...
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| Veröffentlicht in: | Acta biomaterialia 2019-08, Vol.94, p.351-360 |
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| creator | Lee, Kyeong-Min Kim, Jung-Hee Choi, Eun-Sook Kim, Eunjoo Choi, Seong-Kyoon Jeon, Won Bae |
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Successful islet transplantation critically depends on the isolation of healthy islets. However, the islet isolation procedure itself contributes to islet death due to the destruction of intra- and peri-islet extracellular matrices (ECMs) during digestion. We investigated whether an RGD-containing elastin-like polypeptide (REP) could function as a self-assembling matrix to replenish ECMs and protects islets from cell death. Immediately following isolation, islets were coated with REP coacervate particles via isothermal adsorption of an REP solution followed by thermal gelation. REP-coated islets displayed increased viability and insulin secretory capacity in pretransplant culture compared to untreated islets. Co-transplantation of REP-treated islets and REP beneath the renal sub-capsule in streptozotocin-induced diabetic mice restored normoglycemia and serum insulin levels. Mice that received co-transplants maintained normoglycemia for a longer period of time than those receiving untreated islets without REP. Moreover, co-transplantation sites exhibited enhanced β-cell proliferation and vascularization. Thus, the REP-based coacervation strategy improve the survival, function and therapeutic potential of transplanted islets.
1). An artificial matrix polypeptide comprised of thermoresponsive elastin-like peptides and integrin-stimulatory RGD ligands (REP) to reconstitute damaged or lost matrices.
2). Through body temperature-induced coacervation, REP reconstitutes intra-islet environment and enhances islet viability and insulin secretion by activating the pro-survival and insulin signaling pathways.
3). REP-coated islets were transplanted together with the matrix polypeptide under the kidney sub-capsule of mice, it develops a new peri-insular environment, which protects the islet grafts from immune rejection thus extending islet longevity.
4). Our data suggest that in situ self-assembly of biomimetic islet environments become a new platform allowing for improved islet transplantation at extrahepatic sites. |
| doi_str_mv | 10.1016/j.actbio.2019.06.011 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2246243981</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1742706119304210</els_id><sourcerecordid>2273188919</sourcerecordid><originalsourceid>FETCH-LOGICAL-c473t-7b700190e33fd9ff050dfe756263cbf1faad2d388c6aa03070e679b163f6ed0e3</originalsourceid><addsrcrecordid>eNp9kU-L1TAUxYMozjj6DUQKbty05k8nSTeCjDoKA4LoOqbJjdxnm9QkHZhvbx5vdOHCVQL5nZtzzyHkOaMDo0y-PgzW1RnTwCmbBioHytgDcs600r26lPphu6uR94pKdkaelHKgVGjG9WNyJhinDVfn5PuX63e9S7FajBh_dLDYUjH2C_6EbkvL3QZbRQ8drltOt1A6LAvUrmYby7bYJqyYYpf26tJ6fI6dRztDRdet6OApeRTsUuDZ_XlBvn14__XqY3_z-frT1dub3o1K1F7NqjmaKAgR_BQCvaQ-QNuDS-HmwIK1nnuhtZPWUkEVBammmUkRJPgmuyCvTnObzV87lGpWLA6WZhHSXgzno-SjmDRr6Mt_0EPac2zuGqUE03piU6PGE-VyKiVDMFvG1eY7w6g5NmAO5tSAOTZgqDQt0iZ7cT98n1fwf0V_Im_AmxMALY1bhGyKQ4gOPGZw1fiE___hN5WNmfY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2273188919</pqid></control><display><type>article</type><title>RGD-containing elastin-like polypeptide improves islet transplantation outcomes in diabetic mice</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Lee, Kyeong-Min ; Kim, Jung-Hee ; Choi, Eun-Sook ; Kim, Eunjoo ; Choi, Seong-Kyoon ; Jeon, Won Bae</creator><creatorcontrib>Lee, Kyeong-Min ; Kim, Jung-Hee ; Choi, Eun-Sook ; Kim, Eunjoo ; Choi, Seong-Kyoon ; Jeon, Won Bae</creatorcontrib><description>[Display omitted]
Successful islet transplantation critically depends on the isolation of healthy islets. However, the islet isolation procedure itself contributes to islet death due to the destruction of intra- and peri-islet extracellular matrices (ECMs) during digestion. We investigated whether an RGD-containing elastin-like polypeptide (REP) could function as a self-assembling matrix to replenish ECMs and protects islets from cell death. Immediately following isolation, islets were coated with REP coacervate particles via isothermal adsorption of an REP solution followed by thermal gelation. REP-coated islets displayed increased viability and insulin secretory capacity in pretransplant culture compared to untreated islets. Co-transplantation of REP-treated islets and REP beneath the renal sub-capsule in streptozotocin-induced diabetic mice restored normoglycemia and serum insulin levels. Mice that received co-transplants maintained normoglycemia for a longer period of time than those receiving untreated islets without REP. Moreover, co-transplantation sites exhibited enhanced β-cell proliferation and vascularization. Thus, the REP-based coacervation strategy improve the survival, function and therapeutic potential of transplanted islets.
1). An artificial matrix polypeptide comprised of thermoresponsive elastin-like peptides and integrin-stimulatory RGD ligands (REP) to reconstitute damaged or lost matrices.
2). Through body temperature-induced coacervation, REP reconstitutes intra-islet environment and enhances islet viability and insulin secretion by activating the pro-survival and insulin signaling pathways.
3). REP-coated islets were transplanted together with the matrix polypeptide under the kidney sub-capsule of mice, it develops a new peri-insular environment, which protects the islet grafts from immune rejection thus extending islet longevity.
4). Our data suggest that in situ self-assembly of biomimetic islet environments become a new platform allowing for improved islet transplantation at extrahepatic sites.</description><identifier>ISSN: 1742-7061</identifier><identifier>EISSN: 1878-7568</identifier><identifier>DOI: 10.1016/j.actbio.2019.06.011</identifier><identifier>PMID: 31200117</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Blood Glucose - metabolism ; Cell culture ; Cell death ; Cell Line ; Cell Proliferation ; Cell Survival ; Coacervation ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Experimental ; Elastin ; Elastin - chemistry ; Gelation ; Gene Expression Regulation ; Insulin ; Insulin - metabolism ; Insulin secretion ; Insulin Secretion - drug effects ; Islet cells ; Islet survival ; Islet transplantation ; Islets of Langerhans - cytology ; Islets of Langerhans Transplantation - methods ; Male ; Mice ; Mice, Inbred C57BL ; Oligopeptides - chemistry ; Oligopeptides - metabolism ; Pancreatic islet transplantation ; Polypeptides ; Protein coacervate ; Rats, Sprague-Dawley ; RGD-containing elastin-like polypeptide ; RNA, Messenger - metabolism ; Signal Transduction ; Streptozocin ; Thermal gelation ; Transplantation ; Transplants ; Transplants & implants ; Treatment Outcome ; Vascularization ; Viability</subject><ispartof>Acta biomaterialia, 2019-08, Vol.94, p.351-360</ispartof><rights>2019 Acta Materialia Inc.</rights><rights>Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier BV Aug 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c473t-7b700190e33fd9ff050dfe756263cbf1faad2d388c6aa03070e679b163f6ed0e3</citedby><cites>FETCH-LOGICAL-c473t-7b700190e33fd9ff050dfe756263cbf1faad2d388c6aa03070e679b163f6ed0e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.actbio.2019.06.011$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31200117$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Kyeong-Min</creatorcontrib><creatorcontrib>Kim, Jung-Hee</creatorcontrib><creatorcontrib>Choi, Eun-Sook</creatorcontrib><creatorcontrib>Kim, Eunjoo</creatorcontrib><creatorcontrib>Choi, Seong-Kyoon</creatorcontrib><creatorcontrib>Jeon, Won Bae</creatorcontrib><title>RGD-containing elastin-like polypeptide improves islet transplantation outcomes in diabetic mice</title><title>Acta biomaterialia</title><addtitle>Acta Biomater</addtitle><description>[Display omitted]
Successful islet transplantation critically depends on the isolation of healthy islets. However, the islet isolation procedure itself contributes to islet death due to the destruction of intra- and peri-islet extracellular matrices (ECMs) during digestion. We investigated whether an RGD-containing elastin-like polypeptide (REP) could function as a self-assembling matrix to replenish ECMs and protects islets from cell death. Immediately following isolation, islets were coated with REP coacervate particles via isothermal adsorption of an REP solution followed by thermal gelation. REP-coated islets displayed increased viability and insulin secretory capacity in pretransplant culture compared to untreated islets. Co-transplantation of REP-treated islets and REP beneath the renal sub-capsule in streptozotocin-induced diabetic mice restored normoglycemia and serum insulin levels. Mice that received co-transplants maintained normoglycemia for a longer period of time than those receiving untreated islets without REP. Moreover, co-transplantation sites exhibited enhanced β-cell proliferation and vascularization. Thus, the REP-based coacervation strategy improve the survival, function and therapeutic potential of transplanted islets.
1). An artificial matrix polypeptide comprised of thermoresponsive elastin-like peptides and integrin-stimulatory RGD ligands (REP) to reconstitute damaged or lost matrices.
2). Through body temperature-induced coacervation, REP reconstitutes intra-islet environment and enhances islet viability and insulin secretion by activating the pro-survival and insulin signaling pathways.
3). REP-coated islets were transplanted together with the matrix polypeptide under the kidney sub-capsule of mice, it develops a new peri-insular environment, which protects the islet grafts from immune rejection thus extending islet longevity.
4). Our data suggest that in situ self-assembly of biomimetic islet environments become a new platform allowing for improved islet transplantation at extrahepatic sites.</description><subject>Animals</subject><subject>Blood Glucose - metabolism</subject><subject>Cell culture</subject><subject>Cell death</subject><subject>Cell Line</subject><subject>Cell Proliferation</subject><subject>Cell Survival</subject><subject>Coacervation</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Experimental</subject><subject>Elastin</subject><subject>Elastin - chemistry</subject><subject>Gelation</subject><subject>Gene Expression Regulation</subject><subject>Insulin</subject><subject>Insulin - metabolism</subject><subject>Insulin secretion</subject><subject>Insulin Secretion - drug effects</subject><subject>Islet cells</subject><subject>Islet survival</subject><subject>Islet transplantation</subject><subject>Islets of Langerhans - cytology</subject><subject>Islets of Langerhans Transplantation - methods</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Oligopeptides - chemistry</subject><subject>Oligopeptides - metabolism</subject><subject>Pancreatic islet transplantation</subject><subject>Polypeptides</subject><subject>Protein coacervate</subject><subject>Rats, Sprague-Dawley</subject><subject>RGD-containing elastin-like polypeptide</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal Transduction</subject><subject>Streptozocin</subject><subject>Thermal gelation</subject><subject>Transplantation</subject><subject>Transplants</subject><subject>Transplants & implants</subject><subject>Treatment Outcome</subject><subject>Vascularization</subject><subject>Viability</subject><issn>1742-7061</issn><issn>1878-7568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU-L1TAUxYMozjj6DUQKbty05k8nSTeCjDoKA4LoOqbJjdxnm9QkHZhvbx5vdOHCVQL5nZtzzyHkOaMDo0y-PgzW1RnTwCmbBioHytgDcs600r26lPphu6uR94pKdkaelHKgVGjG9WNyJhinDVfn5PuX63e9S7FajBh_dLDYUjH2C_6EbkvL3QZbRQ8drltOt1A6LAvUrmYby7bYJqyYYpf26tJ6fI6dRztDRdet6OApeRTsUuDZ_XlBvn14__XqY3_z-frT1dub3o1K1F7NqjmaKAgR_BQCvaQ-QNuDS-HmwIK1nnuhtZPWUkEVBammmUkRJPgmuyCvTnObzV87lGpWLA6WZhHSXgzno-SjmDRr6Mt_0EPac2zuGqUE03piU6PGE-VyKiVDMFvG1eY7w6g5NmAO5tSAOTZgqDQt0iZ7cT98n1fwf0V_Im_AmxMALY1bhGyKQ4gOPGZw1fiE___hN5WNmfY</recordid><startdate>20190801</startdate><enddate>20190801</enddate><creator>Lee, Kyeong-Min</creator><creator>Kim, Jung-Hee</creator><creator>Choi, Eun-Sook</creator><creator>Kim, Eunjoo</creator><creator>Choi, Seong-Kyoon</creator><creator>Jeon, Won Bae</creator><general>Elsevier Ltd</general><general>Elsevier BV</general><scope>6I.</scope><scope>AAFTH</scope><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>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20190801</creationdate><title>RGD-containing elastin-like polypeptide improves islet transplantation outcomes in diabetic mice</title><author>Lee, Kyeong-Min ; Kim, Jung-Hee ; Choi, Eun-Sook ; Kim, Eunjoo ; Choi, Seong-Kyoon ; Jeon, Won Bae</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c473t-7b700190e33fd9ff050dfe756263cbf1faad2d388c6aa03070e679b163f6ed0e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Blood Glucose - metabolism</topic><topic>Cell culture</topic><topic>Cell death</topic><topic>Cell Line</topic><topic>Cell Proliferation</topic><topic>Cell Survival</topic><topic>Coacervation</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Experimental</topic><topic>Elastin</topic><topic>Elastin - chemistry</topic><topic>Gelation</topic><topic>Gene Expression Regulation</topic><topic>Insulin</topic><topic>Insulin - metabolism</topic><topic>Insulin secretion</topic><topic>Insulin Secretion - drug effects</topic><topic>Islet cells</topic><topic>Islet survival</topic><topic>Islet transplantation</topic><topic>Islets of Langerhans - cytology</topic><topic>Islets of Langerhans Transplantation - methods</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Oligopeptides - chemistry</topic><topic>Oligopeptides - metabolism</topic><topic>Pancreatic islet transplantation</topic><topic>Polypeptides</topic><topic>Protein coacervate</topic><topic>Rats, Sprague-Dawley</topic><topic>RGD-containing elastin-like polypeptide</topic><topic>RNA, Messenger - metabolism</topic><topic>Signal Transduction</topic><topic>Streptozocin</topic><topic>Thermal gelation</topic><topic>Transplantation</topic><topic>Transplants</topic><topic>Transplants & implants</topic><topic>Treatment Outcome</topic><topic>Vascularization</topic><topic>Viability</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Kyeong-Min</creatorcontrib><creatorcontrib>Kim, Jung-Hee</creatorcontrib><creatorcontrib>Choi, Eun-Sook</creatorcontrib><creatorcontrib>Kim, Eunjoo</creatorcontrib><creatorcontrib>Choi, Seong-Kyoon</creatorcontrib><creatorcontrib>Jeon, Won Bae</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Acta biomaterialia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Kyeong-Min</au><au>Kim, Jung-Hee</au><au>Choi, Eun-Sook</au><au>Kim, Eunjoo</au><au>Choi, Seong-Kyoon</au><au>Jeon, Won Bae</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RGD-containing elastin-like polypeptide improves islet transplantation outcomes in diabetic mice</atitle><jtitle>Acta biomaterialia</jtitle><addtitle>Acta Biomater</addtitle><date>2019-08-01</date><risdate>2019</risdate><volume>94</volume><spage>351</spage><epage>360</epage><pages>351-360</pages><issn>1742-7061</issn><eissn>1878-7568</eissn><abstract>[Display omitted]
Successful islet transplantation critically depends on the isolation of healthy islets. However, the islet isolation procedure itself contributes to islet death due to the destruction of intra- and peri-islet extracellular matrices (ECMs) during digestion. We investigated whether an RGD-containing elastin-like polypeptide (REP) could function as a self-assembling matrix to replenish ECMs and protects islets from cell death. Immediately following isolation, islets were coated with REP coacervate particles via isothermal adsorption of an REP solution followed by thermal gelation. REP-coated islets displayed increased viability and insulin secretory capacity in pretransplant culture compared to untreated islets. Co-transplantation of REP-treated islets and REP beneath the renal sub-capsule in streptozotocin-induced diabetic mice restored normoglycemia and serum insulin levels. Mice that received co-transplants maintained normoglycemia for a longer period of time than those receiving untreated islets without REP. Moreover, co-transplantation sites exhibited enhanced β-cell proliferation and vascularization. Thus, the REP-based coacervation strategy improve the survival, function and therapeutic potential of transplanted islets.
1). An artificial matrix polypeptide comprised of thermoresponsive elastin-like peptides and integrin-stimulatory RGD ligands (REP) to reconstitute damaged or lost matrices.
2). Through body temperature-induced coacervation, REP reconstitutes intra-islet environment and enhances islet viability and insulin secretion by activating the pro-survival and insulin signaling pathways.
3). REP-coated islets were transplanted together with the matrix polypeptide under the kidney sub-capsule of mice, it develops a new peri-insular environment, which protects the islet grafts from immune rejection thus extending islet longevity.
4). Our data suggest that in situ self-assembly of biomimetic islet environments become a new platform allowing for improved islet transplantation at extrahepatic sites.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>31200117</pmid><doi>10.1016/j.actbio.2019.06.011</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Animals Blood Glucose - metabolism Cell culture Cell death Cell Line Cell Proliferation Cell Survival Coacervation Diabetes Diabetes mellitus Diabetes Mellitus, Experimental Elastin Elastin - chemistry Gelation Gene Expression Regulation Insulin Insulin - metabolism Insulin secretion Insulin Secretion - drug effects Islet cells Islet survival Islet transplantation Islets of Langerhans - cytology Islets of Langerhans Transplantation - methods Male Mice Mice, Inbred C57BL Oligopeptides - chemistry Oligopeptides - metabolism Pancreatic islet transplantation Polypeptides Protein coacervate Rats, Sprague-Dawley RGD-containing elastin-like polypeptide RNA, Messenger - metabolism Signal Transduction Streptozocin Thermal gelation Transplantation Transplants Transplants & implants Treatment Outcome Vascularization Viability |
| title | RGD-containing elastin-like polypeptide improves islet transplantation outcomes in diabetic mice |
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