Reversal of Diabetes by the Creation of Neo-Islet Tissues Into a Subcutaneous Site Using Islet Cell Sheets

There remains a paucity of therapeutic approaches to completely treat diabetes mellitus. This study was designed to develop a dispersed islet cell-based tissue engineering approach to engineer functional neo-islet tissues in the absence of traditional bioabsorbable scaffold matrices. Specialized coa...

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Veröffentlicht in:Transplantation 2011-12, Vol.92 (11), p.1231-1236
Hauptverfasser: SAITO, Takahiro, OHASHI, Kazuo, UTOH, Rie, SHIMIZU, Hirofumi, ISE, Kazuya, SUZUKI, Hiroyuki, YAMATO, Masayuki, OKANO, Teruo, GOTOH, Mitsukazu
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container_end_page 1236
container_issue 11
container_start_page 1231
container_title Transplantation
container_volume 92
creator SAITO, Takahiro
OHASHI, Kazuo
UTOH, Rie
SHIMIZU, Hirofumi
ISE, Kazuya
SUZUKI, Hiroyuki
YAMATO, Masayuki
OKANO, Teruo
GOTOH, Mitsukazu
description There remains a paucity of therapeutic approaches to completely treat diabetes mellitus. This study was designed to develop a dispersed islet cell-based tissue engineering approach to engineer functional neo-islet tissues in the absence of traditional bioabsorbable scaffold matrices. Specialized coated plastic dishes were prepared by covalently immobilizing a temperature-responsive polymer, poly(N-isopropylacrylamide), onto the plastic followed by coating with laminin-5. Dispersed rat islet cells were plated on the laminin-5-poly(N-isopropylacrylamide) dishes. After 2 days of culturing, islet cells were harvested as a uniformly connected tissue sheet by lowering the culture temperature from 37°C to 20°C for 30 min. Two harvested islet cell sheets were transplanted into the subcutaneous space of streptozotocin-induced diabetic severe combined immunodeficiency (SCID) mice to engineer neo-islet tissues in vivo. Therapeutic effects were investigated after the tissue engineering procedures. In all of the diabetic SCID mice transplanted with the islet sheets, serum hyperglycemia was successfully reverted to a steady normoglycemic level. The recipient SCID mice demonstrated positive for serum rat C-peptide and elevated serum insulin levels. Moreover, the islet cell sheet-transplanted SCID mice demonstrated rapid glucose clearance and return of serum glucose levels after intraperitoneal glucose tolerance test. Histological examination revealed that the transplanted islet cell sheets were structured as flat clusters of islet tissues in which an active vascular network manifested within and surrounding the newly formed tissues. This study describes a new proof-of-concept therapeutic approach to engineer functional neo-islet tissues for the treatment of type 1 diabetes mellitus.
doi_str_mv 10.1097/TP.0b013e3182375835
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This study was designed to develop a dispersed islet cell-based tissue engineering approach to engineer functional neo-islet tissues in the absence of traditional bioabsorbable scaffold matrices. Specialized coated plastic dishes were prepared by covalently immobilizing a temperature-responsive polymer, poly(N-isopropylacrylamide), onto the plastic followed by coating with laminin-5. Dispersed rat islet cells were plated on the laminin-5-poly(N-isopropylacrylamide) dishes. After 2 days of culturing, islet cells were harvested as a uniformly connected tissue sheet by lowering the culture temperature from 37°C to 20°C for 30 min. Two harvested islet cell sheets were transplanted into the subcutaneous space of streptozotocin-induced diabetic severe combined immunodeficiency (SCID) mice to engineer neo-islet tissues in vivo. Therapeutic effects were investigated after the tissue engineering procedures. In all of the diabetic SCID mice transplanted with the islet sheets, serum hyperglycemia was successfully reverted to a steady normoglycemic level. The recipient SCID mice demonstrated positive for serum rat C-peptide and elevated serum insulin levels. Moreover, the islet cell sheet-transplanted SCID mice demonstrated rapid glucose clearance and return of serum glucose levels after intraperitoneal glucose tolerance test. Histological examination revealed that the transplanted islet cell sheets were structured as flat clusters of islet tissues in which an active vascular network manifested within and surrounding the newly formed tissues. 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This study was designed to develop a dispersed islet cell-based tissue engineering approach to engineer functional neo-islet tissues in the absence of traditional bioabsorbable scaffold matrices. Specialized coated plastic dishes were prepared by covalently immobilizing a temperature-responsive polymer, poly(N-isopropylacrylamide), onto the plastic followed by coating with laminin-5. Dispersed rat islet cells were plated on the laminin-5-poly(N-isopropylacrylamide) dishes. After 2 days of culturing, islet cells were harvested as a uniformly connected tissue sheet by lowering the culture temperature from 37°C to 20°C for 30 min. Two harvested islet cell sheets were transplanted into the subcutaneous space of streptozotocin-induced diabetic severe combined immunodeficiency (SCID) mice to engineer neo-islet tissues in vivo. Therapeutic effects were investigated after the tissue engineering procedures. 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Graft diseases</subject><subject>Temperature effects</subject><subject>Tissue engineering</subject><subject>Tissue Engineering - methods</subject><subject>Tissue Scaffolds</subject><subject>Tissue, organ and graft immunology</subject><subject>Treatment Outcome</subject><issn>0041-1337</issn><issn>1534-6080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90U1Lw0AQBuBFFFurv0CQvYheUmd3ss3mKPGrIFpsew6bZGJT0qRmN0L_vSmtCh48zWGe2XnZYexcwFBAGNzMJkNIQCCh0BIDpVEdsL5Q6Hsj0HDI-gC-8ARi0GMn1i4BQGEQHLOelEL6Uss-W77RJzXWlLzO-V1hEnJkebLhbkE8asi4oq62vReqvbEtyfFZYW3boXHlam74tE3S1pmK6tbyaeGIz21RvfMdjqgs-XRB5OwpO8pNaelsXwds_nA_i56859fHcXT77KW-kM7LswARtSCpcxB-KLVSWuUYaiOkUmYUGhSUJRkkgQ_aSAo1Zhp8KdIElcQBu9q9u27qjy6oi1eFTbscu4xxCAHgyFeik9f_SgGgdbcYtxR3NG1qaxvK43VTrEyz6VC8PUc8m8R_z9FNXewXtMmKsp-Z7__vwOUeGJuaMm9MlRb21ympR1IBfgFwtpC-</recordid><startdate>20111215</startdate><enddate>20111215</enddate><creator>SAITO, Takahiro</creator><creator>OHASHI, Kazuo</creator><creator>UTOH, Rie</creator><creator>SHIMIZU, Hirofumi</creator><creator>ISE, Kazuya</creator><creator>SUZUKI, Hiroyuki</creator><creator>YAMATO, Masayuki</creator><creator>OKANO, Teruo</creator><creator>GOTOH, Mitsukazu</creator><general>Lippincott Williams &amp; Wilkins</general><scope>IQODW</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20111215</creationdate><title>Reversal of Diabetes by the Creation of Neo-Islet Tissues Into a Subcutaneous Site Using Islet Cell Sheets</title><author>SAITO, Takahiro ; OHASHI, Kazuo ; UTOH, Rie ; SHIMIZU, Hirofumi ; ISE, Kazuya ; SUZUKI, Hiroyuki ; YAMATO, Masayuki ; OKANO, Teruo ; GOTOH, Mitsukazu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-fd733381e28f0149285585f398a1255a69a31edbd0b7408a2e983d80421cb3523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Allografts</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood Glucose - metabolism</topic><topic>C-Peptide - blood</topic><topic>Cell culture</topic><topic>Cells, Cultured</topic><topic>Coatings</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Experimental - blood</topic><topic>Diabetes Mellitus, Experimental - chemically induced</topic><topic>Diabetes Mellitus, Experimental - surgery</topic><topic>Diabetes. 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Graft diseases</topic><topic>Temperature effects</topic><topic>Tissue engineering</topic><topic>Tissue Engineering - methods</topic><topic>Tissue Scaffolds</topic><topic>Tissue, organ and graft immunology</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SAITO, Takahiro</creatorcontrib><creatorcontrib>OHASHI, Kazuo</creatorcontrib><creatorcontrib>UTOH, Rie</creatorcontrib><creatorcontrib>SHIMIZU, Hirofumi</creatorcontrib><creatorcontrib>ISE, Kazuya</creatorcontrib><creatorcontrib>SUZUKI, Hiroyuki</creatorcontrib><creatorcontrib>YAMATO, Masayuki</creatorcontrib><creatorcontrib>OKANO, Teruo</creatorcontrib><creatorcontrib>GOTOH, Mitsukazu</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SAITO, Takahiro</au><au>OHASHI, Kazuo</au><au>UTOH, Rie</au><au>SHIMIZU, Hirofumi</au><au>ISE, Kazuya</au><au>SUZUKI, Hiroyuki</au><au>YAMATO, Masayuki</au><au>OKANO, Teruo</au><au>GOTOH, Mitsukazu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reversal of Diabetes by the Creation of Neo-Islet Tissues Into a Subcutaneous Site Using Islet Cell Sheets</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>2011-12-15</date><risdate>2011</risdate><volume>92</volume><issue>11</issue><spage>1231</spage><epage>1236</epage><pages>1231-1236</pages><issn>0041-1337</issn><eissn>1534-6080</eissn><coden>TRPLAU</coden><abstract>There remains a paucity of therapeutic approaches to completely treat diabetes mellitus. 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In all of the diabetic SCID mice transplanted with the islet sheets, serum hyperglycemia was successfully reverted to a steady normoglycemic level. The recipient SCID mice demonstrated positive for serum rat C-peptide and elevated serum insulin levels. Moreover, the islet cell sheet-transplanted SCID mice demonstrated rapid glucose clearance and return of serum glucose levels after intraperitoneal glucose tolerance test. Histological examination revealed that the transplanted islet cell sheets were structured as flat clusters of islet tissues in which an active vascular network manifested within and surrounding the newly formed tissues. This study describes a new proof-of-concept therapeutic approach to engineer functional neo-islet tissues for the treatment of type 1 diabetes mellitus.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams &amp; Wilkins</pub><pmid>22124282</pmid><doi>10.1097/TP.0b013e3182375835</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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subjects Allografts
Animals
Biological and medical sciences
Blood Glucose - metabolism
C-Peptide - blood
Cell culture
Cells, Cultured
Coatings
Diabetes mellitus
Diabetes Mellitus, Experimental - blood
Diabetes Mellitus, Experimental - chemically induced
Diabetes Mellitus, Experimental - surgery
Diabetes. Impaired glucose tolerance
Disease Models, Animal
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Glucose tolerance
Hyperglycemia
Insulin
Insulin - blood
Islet cells
Islets of Langerhans
Islets of Langerhans - cytology
Islets of Langerhans - surgery
Islets of Langerhans Transplantation - methods
Male
Medical sciences
Mice
Mice, SCID
Pancreas
Plastics
Rats
Rats, Inbred Lew
scaffolds
Streptozocin - adverse effects
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Temperature effects
Tissue engineering
Tissue Engineering - methods
Tissue Scaffolds
Tissue, organ and graft immunology
Treatment Outcome
title Reversal of Diabetes by the Creation of Neo-Islet Tissues Into a Subcutaneous Site Using Islet Cell Sheets
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