Loading…
The Spleen Is an Ideal Site for Inducing Transplanted Islet Graft Expansion in Mice
Alternative islet transplantation sites have the potential to reduce the marginal number of islets required to ameliorate hyperglycemia in recipients with diabetes. Previously, we reported that T cell leukemia homeobox 1 (Tlx1)+ stem cells in the spleen effectively regenerated into insulin-producing...
Saved in:
Published in: | PloS one 2017-01, Vol.12 (1), p.e0170899 |
---|---|
Main Authors: | , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c791t-3379a62d7cf92326a7724002b1352a3788058be0d0235e4082691ff6ef5dcad13 |
---|---|
cites | cdi_FETCH-LOGICAL-c791t-3379a62d7cf92326a7724002b1352a3788058be0d0235e4082691ff6ef5dcad13 |
container_end_page | |
container_issue | 1 |
container_start_page | e0170899 |
container_title | PloS one |
container_volume | 12 |
creator | Itoh, Takeshi Nishinakamura, Hitomi Kumano, Kenjiro Takahashi, Hiroyuki Kodama, Shohta |
description | Alternative islet transplantation sites have the potential to reduce the marginal number of islets required to ameliorate hyperglycemia in recipients with diabetes. Previously, we reported that T cell leukemia homeobox 1 (Tlx1)+ stem cells in the spleen effectively regenerated into insulin-producing cells in the pancreas of non-obese diabetic mice with end-stage disease. Thus, we investigated the spleen as a potential alternative islet transplantation site. Streptozotocin-induced diabetic C57BL/6 mice received syngeneic islets into the portal vein (PV), beneath the kidney capsule (KC), or into the spleen (SP). The marginal number of islets by PV, KC, or SP was 200, 100, and 50, respectively. Some plasma inflammatory cytokine levels in the SP group were significantly lower than those of the PV group after receiving a marginal number of islets, indicating reduced inflammation in the SP group. Insulin contents were increased 280 days after islet transplantation compared with those immediately following transplantation (p |
doi_str_mv | 10.1371/journal.pone.0170899 |
format | article |
fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1862998591</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A479360641</galeid><doaj_id>oai_doaj_org_article_2251b1853b3142569a57fa25dff569c6</doaj_id><sourcerecordid>A479360641</sourcerecordid><originalsourceid>FETCH-LOGICAL-c791t-3379a62d7cf92326a7724002b1352a3788058be0d0235e4082691ff6ef5dcad13</originalsourceid><addsrcrecordid>eNqNk1trFDEUxwdRbK1-A9EBQfRh11wmtxehlFoXKgV39TVkM8luyuxkmmSkfnsz3WnZkT6UQK6_88_JyTlF8RaCOcQMfrn2fWhVM-98a-YAMsCFeFYcQ4HRjCKAnx_Mj4pXMV4DQDCn9GVxhDjEBHF8XCxXW1Muu8aYtlzEUuW-Nqoply6Z0vpQLtq6167dlKug2tg1qk2mzmhjUnkRlE3l-W2XT5xvS9eWP5w2r4sXVjXRvBnHk-LXt_PV2ffZ5dXF4uz0cqaZgGmGMROKopppKxBGVDGGKgDQevBNYcY5IHxtQA0QJqYCHFEBraXGklqrGuKT4v1et2t8lGM8ooScIiE4EQOx2BO1V9eyC26nwl_plZN3Gz5spArJ6cZIhAhcQ07wGsMKESoUYVYhUlubF5pmra_jbf16Z2pt2hRUMxGdnrRuKzf-jySICcZBFvg0CgR_05uY5M5FbZocUuP7O785zjcT8RQUI5T9HFQ__Ic-HoiR2qj8Vtdan13Ug6g8rZjAFNBqoOaPULnVZud0zjPr8v7E4PPEIDPJ3KaN6mOUi-XPp7NXv6fsxwN2mxMybaNv-pSzLE7Bag_q4GMMxj78BwRyKJP7aMihTORYJtns3eFfPhjd1wX-B0OjCP8</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1862998591</pqid></control><display><type>article</type><title>The Spleen Is an Ideal Site for Inducing Transplanted Islet Graft Expansion in Mice</title><source>Publicly Available Content Database</source><source>PubMed Central</source><creator>Itoh, Takeshi ; Nishinakamura, Hitomi ; Kumano, Kenjiro ; Takahashi, Hiroyuki ; Kodama, Shohta</creator><contributor>Fiorina, Paolo</contributor><creatorcontrib>Itoh, Takeshi ; Nishinakamura, Hitomi ; Kumano, Kenjiro ; Takahashi, Hiroyuki ; Kodama, Shohta ; Fiorina, Paolo</creatorcontrib><description>Alternative islet transplantation sites have the potential to reduce the marginal number of islets required to ameliorate hyperglycemia in recipients with diabetes. Previously, we reported that T cell leukemia homeobox 1 (Tlx1)+ stem cells in the spleen effectively regenerated into insulin-producing cells in the pancreas of non-obese diabetic mice with end-stage disease. Thus, we investigated the spleen as a potential alternative islet transplantation site. Streptozotocin-induced diabetic C57BL/6 mice received syngeneic islets into the portal vein (PV), beneath the kidney capsule (KC), or into the spleen (SP). The marginal number of islets by PV, KC, or SP was 200, 100, and 50, respectively. Some plasma inflammatory cytokine levels in the SP group were significantly lower than those of the PV group after receiving a marginal number of islets, indicating reduced inflammation in the SP group. Insulin contents were increased 280 days after islet transplantation compared with those immediately following transplantation (p<0.05). Additionally, Tlx1-related genes, including Rrm2b and Pla2g2d, were up-regulated, which indicates that islet grafts expanded in the spleen. The spleen is an ideal candidate for an alternative islet transplantation site because of the resulting reduced inflammation and expansion of the islet graft.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0170899</identifier><identifier>PMID: 28135283</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Biology and Life Sciences ; Chemokines - blood ; Cloning ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Experimental - therapy ; Gene Expression Regulation ; Glucose ; Glucose Tolerance Test ; Grafting ; Grafts ; Homeobox ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Hospitals ; Hyperglycemia ; Inflammation ; Inflammation - pathology ; Insulin ; Islet cell transplantation ; Islet cells ; Islets of Langerhans Transplantation ; Kidney - physiology ; Kidneys ; Leukemia ; Liver - physiology ; Liver transplants ; Lymphocytes T ; Male ; Medicine ; Medicine and Health Sciences ; Mice ; Mice, Inbred C57BL ; Pancreas ; Pancreatic islet transplantation ; Physiological aspects ; Portal vein ; Portal Vein - physiology ; Rodents ; Spleen ; Spleen - physiology ; Stem cell transplantation ; Stem cells ; Streptozocin ; Studies ; Syngeneic grafts ; Time Factors ; Tlx1 protein ; Transplantation ; Transplants & implants</subject><ispartof>PloS one, 2017-01, Vol.12 (1), p.e0170899</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Itoh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Itoh et al 2017 Itoh et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c791t-3379a62d7cf92326a7724002b1352a3788058be0d0235e4082691ff6ef5dcad13</citedby><cites>FETCH-LOGICAL-c791t-3379a62d7cf92326a7724002b1352a3788058be0d0235e4082691ff6ef5dcad13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1862998591/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1862998591?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25751,27922,27923,37010,37011,44588,53789,53791,74896</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28135283$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Fiorina, Paolo</contributor><creatorcontrib>Itoh, Takeshi</creatorcontrib><creatorcontrib>Nishinakamura, Hitomi</creatorcontrib><creatorcontrib>Kumano, Kenjiro</creatorcontrib><creatorcontrib>Takahashi, Hiroyuki</creatorcontrib><creatorcontrib>Kodama, Shohta</creatorcontrib><title>The Spleen Is an Ideal Site for Inducing Transplanted Islet Graft Expansion in Mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Alternative islet transplantation sites have the potential to reduce the marginal number of islets required to ameliorate hyperglycemia in recipients with diabetes. Previously, we reported that T cell leukemia homeobox 1 (Tlx1)+ stem cells in the spleen effectively regenerated into insulin-producing cells in the pancreas of non-obese diabetic mice with end-stage disease. Thus, we investigated the spleen as a potential alternative islet transplantation site. Streptozotocin-induced diabetic C57BL/6 mice received syngeneic islets into the portal vein (PV), beneath the kidney capsule (KC), or into the spleen (SP). The marginal number of islets by PV, KC, or SP was 200, 100, and 50, respectively. Some plasma inflammatory cytokine levels in the SP group were significantly lower than those of the PV group after receiving a marginal number of islets, indicating reduced inflammation in the SP group. Insulin contents were increased 280 days after islet transplantation compared with those immediately following transplantation (p<0.05). Additionally, Tlx1-related genes, including Rrm2b and Pla2g2d, were up-regulated, which indicates that islet grafts expanded in the spleen. The spleen is an ideal candidate for an alternative islet transplantation site because of the resulting reduced inflammation and expansion of the islet graft.</description><subject>Animals</subject><subject>Biology and Life Sciences</subject><subject>Chemokines - blood</subject><subject>Cloning</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Experimental - therapy</subject><subject>Gene Expression Regulation</subject><subject>Glucose</subject><subject>Glucose Tolerance Test</subject><subject>Grafting</subject><subject>Grafts</subject><subject>Homeobox</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Hospitals</subject><subject>Hyperglycemia</subject><subject>Inflammation</subject><subject>Inflammation - pathology</subject><subject>Insulin</subject><subject>Islet cell transplantation</subject><subject>Islet cells</subject><subject>Islets of Langerhans Transplantation</subject><subject>Kidney - physiology</subject><subject>Kidneys</subject><subject>Leukemia</subject><subject>Liver - physiology</subject><subject>Liver transplants</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Pancreas</subject><subject>Pancreatic islet transplantation</subject><subject>Physiological aspects</subject><subject>Portal vein</subject><subject>Portal Vein - physiology</subject><subject>Rodents</subject><subject>Spleen</subject><subject>Spleen - physiology</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Streptozocin</subject><subject>Studies</subject><subject>Syngeneic grafts</subject><subject>Time Factors</subject><subject>Tlx1 protein</subject><subject>Transplantation</subject><subject>Transplants & implants</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1trFDEUxwdRbK1-A9EBQfRh11wmtxehlFoXKgV39TVkM8luyuxkmmSkfnsz3WnZkT6UQK6_88_JyTlF8RaCOcQMfrn2fWhVM-98a-YAMsCFeFYcQ4HRjCKAnx_Mj4pXMV4DQDCn9GVxhDjEBHF8XCxXW1Muu8aYtlzEUuW-Nqoply6Z0vpQLtq6167dlKug2tg1qk2mzmhjUnkRlE3l-W2XT5xvS9eWP5w2r4sXVjXRvBnHk-LXt_PV2ffZ5dXF4uz0cqaZgGmGMROKopppKxBGVDGGKgDQevBNYcY5IHxtQA0QJqYCHFEBraXGklqrGuKT4v1et2t8lGM8ooScIiE4EQOx2BO1V9eyC26nwl_plZN3Gz5spArJ6cZIhAhcQ07wGsMKESoUYVYhUlubF5pmra_jbf16Z2pt2hRUMxGdnrRuKzf-jySICcZBFvg0CgR_05uY5M5FbZocUuP7O785zjcT8RQUI5T9HFQ__Ic-HoiR2qj8Vtdan13Ug6g8rZjAFNBqoOaPULnVZud0zjPr8v7E4PPEIDPJ3KaN6mOUi-XPp7NXv6fsxwN2mxMybaNv-pSzLE7Bag_q4GMMxj78BwRyKJP7aMihTORYJtns3eFfPhjd1wX-B0OjCP8</recordid><startdate>20170130</startdate><enddate>20170130</enddate><creator>Itoh, Takeshi</creator><creator>Nishinakamura, Hitomi</creator><creator>Kumano, Kenjiro</creator><creator>Takahashi, Hiroyuki</creator><creator>Kodama, Shohta</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20170130</creationdate><title>The Spleen Is an Ideal Site for Inducing Transplanted Islet Graft Expansion in Mice</title><author>Itoh, Takeshi ; Nishinakamura, Hitomi ; Kumano, Kenjiro ; Takahashi, Hiroyuki ; Kodama, Shohta</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c791t-3379a62d7cf92326a7724002b1352a3788058be0d0235e4082691ff6ef5dcad13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Biology and Life Sciences</topic><topic>Chemokines - blood</topic><topic>Cloning</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Experimental - therapy</topic><topic>Gene Expression Regulation</topic><topic>Glucose</topic><topic>Glucose Tolerance Test</topic><topic>Grafting</topic><topic>Grafts</topic><topic>Homeobox</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Hospitals</topic><topic>Hyperglycemia</topic><topic>Inflammation</topic><topic>Inflammation - pathology</topic><topic>Insulin</topic><topic>Islet cell transplantation</topic><topic>Islet cells</topic><topic>Islets of Langerhans Transplantation</topic><topic>Kidney - physiology</topic><topic>Kidneys</topic><topic>Leukemia</topic><topic>Liver - physiology</topic><topic>Liver transplants</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Pancreas</topic><topic>Pancreatic islet transplantation</topic><topic>Physiological aspects</topic><topic>Portal vein</topic><topic>Portal Vein - physiology</topic><topic>Rodents</topic><topic>Spleen</topic><topic>Spleen - physiology</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Streptozocin</topic><topic>Studies</topic><topic>Syngeneic grafts</topic><topic>Time Factors</topic><topic>Tlx1 protein</topic><topic>Transplantation</topic><topic>Transplants & implants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Itoh, Takeshi</creatorcontrib><creatorcontrib>Nishinakamura, Hitomi</creatorcontrib><creatorcontrib>Kumano, Kenjiro</creatorcontrib><creatorcontrib>Takahashi, Hiroyuki</creatorcontrib><creatorcontrib>Kodama, Shohta</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>ProQuest Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Database (Proquest)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Agriculture Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Itoh, Takeshi</au><au>Nishinakamura, Hitomi</au><au>Kumano, Kenjiro</au><au>Takahashi, Hiroyuki</au><au>Kodama, Shohta</au><au>Fiorina, Paolo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Spleen Is an Ideal Site for Inducing Transplanted Islet Graft Expansion in Mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-01-30</date><risdate>2017</risdate><volume>12</volume><issue>1</issue><spage>e0170899</spage><pages>e0170899-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Alternative islet transplantation sites have the potential to reduce the marginal number of islets required to ameliorate hyperglycemia in recipients with diabetes. Previously, we reported that T cell leukemia homeobox 1 (Tlx1)+ stem cells in the spleen effectively regenerated into insulin-producing cells in the pancreas of non-obese diabetic mice with end-stage disease. Thus, we investigated the spleen as a potential alternative islet transplantation site. Streptozotocin-induced diabetic C57BL/6 mice received syngeneic islets into the portal vein (PV), beneath the kidney capsule (KC), or into the spleen (SP). The marginal number of islets by PV, KC, or SP was 200, 100, and 50, respectively. Some plasma inflammatory cytokine levels in the SP group were significantly lower than those of the PV group after receiving a marginal number of islets, indicating reduced inflammation in the SP group. Insulin contents were increased 280 days after islet transplantation compared with those immediately following transplantation (p<0.05). Additionally, Tlx1-related genes, including Rrm2b and Pla2g2d, were up-regulated, which indicates that islet grafts expanded in the spleen. The spleen is an ideal candidate for an alternative islet transplantation site because of the resulting reduced inflammation and expansion of the islet graft.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28135283</pmid><doi>10.1371/journal.pone.0170899</doi><tpages>e0170899</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2017-01, Vol.12 (1), p.e0170899 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1862998591 |
source | Publicly Available Content Database; PubMed Central |
subjects | Animals Biology and Life Sciences Chemokines - blood Cloning Diabetes Diabetes mellitus Diabetes Mellitus, Experimental - therapy Gene Expression Regulation Glucose Glucose Tolerance Test Grafting Grafts Homeobox Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Hospitals Hyperglycemia Inflammation Inflammation - pathology Insulin Islet cell transplantation Islet cells Islets of Langerhans Transplantation Kidney - physiology Kidneys Leukemia Liver - physiology Liver transplants Lymphocytes T Male Medicine Medicine and Health Sciences Mice Mice, Inbred C57BL Pancreas Pancreatic islet transplantation Physiological aspects Portal vein Portal Vein - physiology Rodents Spleen Spleen - physiology Stem cell transplantation Stem cells Streptozocin Studies Syngeneic grafts Time Factors Tlx1 protein Transplantation Transplants & implants |
title | The Spleen Is an Ideal Site for Inducing Transplanted Islet Graft Expansion in Mice |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-13T19%3A38%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20Spleen%20Is%20an%20Ideal%20Site%20for%20Inducing%20Transplanted%20Islet%20Graft%20Expansion%20in%20Mice&rft.jtitle=PloS%20one&rft.au=Itoh,%20Takeshi&rft.date=2017-01-30&rft.volume=12&rft.issue=1&rft.spage=e0170899&rft.pages=e0170899-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0170899&rft_dat=%3Cgale_plos_%3EA479360641%3C/gale_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c791t-3379a62d7cf92326a7724002b1352a3788058be0d0235e4082691ff6ef5dcad13%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1862998591&rft_id=info:pmid/28135283&rft_galeid=A479360641&rfr_iscdi=true |