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...

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Main Authors: Takeshi Itoh, Hitomi Nishinakamura, Kenjiro Kumano, Hiroyuki Takahashi, Shohta Kodama
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5279780?pdf=render
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author Takeshi Itoh
Hitomi Nishinakamura
Kenjiro Kumano
Hiroyuki Takahashi
Shohta Kodama
author_facet Takeshi Itoh
Hitomi Nishinakamura
Kenjiro Kumano
Hiroyuki Takahashi
Shohta Kodama
author_sort Takeshi Itoh
collection DOAJ
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.
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spelling doaj.art-2251b1853b3142569a57fa25dff569c62022-12-22T01:34:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01121e017089910.1371/journal.pone.0170899The Spleen Is an Ideal Site for Inducing Transplanted Islet Graft Expansion in Mice.Takeshi ItohHitomi NishinakamuraKenjiro KumanoHiroyuki TakahashiShohta KodamaAlternative 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.http://europepmc.org/articles/PMC5279780?pdf=render
spellingShingle Takeshi Itoh
Hitomi Nishinakamura
Kenjiro Kumano
Hiroyuki Takahashi
Shohta Kodama
The Spleen Is an Ideal Site for Inducing Transplanted Islet Graft Expansion in Mice.
PLoS ONE
title The Spleen Is an Ideal Site for Inducing Transplanted Islet Graft Expansion in Mice.
title_full The Spleen Is an Ideal Site for Inducing Transplanted Islet Graft Expansion in Mice.
title_fullStr The Spleen Is an Ideal Site for Inducing Transplanted Islet Graft Expansion in Mice.
title_full_unstemmed The Spleen Is an Ideal Site for Inducing Transplanted Islet Graft Expansion in Mice.
title_short The Spleen Is an Ideal Site for Inducing Transplanted Islet Graft Expansion in Mice.
title_sort spleen is an ideal site for inducing transplanted islet graft expansion in mice
url http://europepmc.org/articles/PMC5279780?pdf=render
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