Brain Death in Combination with Warm Ischemic Stress during Isolation Procedures Induces the Expression of Crucial Inflammatory Mediators in the Isolated Islets

Tissue factor (TF) and monocyte chemoattractant protein-1 (MCP-1) expressed on the islets have been identified as the main trigger of the instant blood-mediated inflammatory reaction (IBMIR) in islet transplantation. Because the key steps that directly induce TF and MCP-1 remain to be determined, we...

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Main Authors: Yukihiko Saito, Masafumi Goto M.D., Ph.D., Kozue Maya, Norihiko Ogawa, Keisei Fujimori, Yoshimochi Kurokawa, Susumu Satomi
Format: Article
Language:English
Published: SAGE Publishing 2010-06-01
Series:Cell Transplantation
Online Access:https://doi.org/10.3727/096368910X508889
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author Yukihiko Saito
Masafumi Goto M.D., Ph.D.
Kozue Maya
Norihiko Ogawa
Keisei Fujimori
Yoshimochi Kurokawa
Susumu Satomi
author_facet Yukihiko Saito
Masafumi Goto M.D., Ph.D.
Kozue Maya
Norihiko Ogawa
Keisei Fujimori
Yoshimochi Kurokawa
Susumu Satomi
author_sort Yukihiko Saito
collection DOAJ
description Tissue factor (TF) and monocyte chemoattractant protein-1 (MCP-1) expressed on the islets have been identified as the main trigger of the instant blood-mediated inflammatory reaction (IBMIR) in islet transplantation. Because the key steps that directly induce TF and MCP-1 remain to be determined, we focused on the influence of brain death (BD) on TF and MCP-1 expression in the pancreatic tissues and isolated islets using a rodent model. TF and MCP-1 mRNA levels in the pancreatic tissues were similar between the BD and the control group. However, TF and MCP-1 mRNA in the fresh islets of the BD group were significantly higher than that of the control group ( p < 0.01). BD may thus be suggested to be of great importance as an initiator of TF and MCP-1 induction in the isolated islets. Furthermore, the upregulation of crucial inflammatory mediators induced by BD could be exacerbated by warm ischemic damage during digestion procedures. In the present study, the islet yield and purity were affected by BD. However, almost no influences were observed with respect to islet viability, indicating that the expression of inflammatory mediators rather than islet viability is more susceptible to BD. According to the change in time course of TF and MCP-1 expression in the isolated islets, the selected time point for islet infusion in current clinical islet transplantation was thus shown to be at its worst level, at least with respect to the damage caused by BD and ischemic stress. In conclusion, BD in combination with warm ischemic stress during isolation procedures induces a high expression of TF and MCP-1 in the isolated islets. In order to reduce the expression of crucial inflammatory mediators in the islet grafts, the management of the pancreas from brain-dead donors with early anti-inflammatory treatments is thus warranted.
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spelling doaj.art-cca7d3d8553043ec81f6b234db5d717f2022-12-22T01:29:53ZengSAGE PublishingCell Transplantation0963-68971555-38922010-06-011910.3727/096368910X508889Brain Death in Combination with Warm Ischemic Stress during Isolation Procedures Induces the Expression of Crucial Inflammatory Mediators in the Isolated IsletsYukihiko Saito0Masafumi Goto M.D., Ph.D.1Kozue Maya2Norihiko Ogawa3Keisei Fujimori4Yoshimochi Kurokawa5Susumu Satomi6Division of Advanced Surgical Science and Technology, Tohoku University, Sendai, JapanTohoku University International Advanced Research and Education Organization, Tohoku University, Sendai, JapanTohoku University International Advanced Research and Education Organization, Tohoku University, Sendai, JapanDivision of Advanced Surgical Science and Technology, Tohoku University, Sendai, JapanMedical Safety Management Office, Tohoku University, Sendai, JapanTohoku University Innovation of New Biomedical Engineering Center, Tohoku University, Sendai, JapanDivision of Advanced Surgical Science and Technology, Tohoku University, Sendai, JapanTissue factor (TF) and monocyte chemoattractant protein-1 (MCP-1) expressed on the islets have been identified as the main trigger of the instant blood-mediated inflammatory reaction (IBMIR) in islet transplantation. Because the key steps that directly induce TF and MCP-1 remain to be determined, we focused on the influence of brain death (BD) on TF and MCP-1 expression in the pancreatic tissues and isolated islets using a rodent model. TF and MCP-1 mRNA levels in the pancreatic tissues were similar between the BD and the control group. However, TF and MCP-1 mRNA in the fresh islets of the BD group were significantly higher than that of the control group ( p < 0.01). BD may thus be suggested to be of great importance as an initiator of TF and MCP-1 induction in the isolated islets. Furthermore, the upregulation of crucial inflammatory mediators induced by BD could be exacerbated by warm ischemic damage during digestion procedures. In the present study, the islet yield and purity were affected by BD. However, almost no influences were observed with respect to islet viability, indicating that the expression of inflammatory mediators rather than islet viability is more susceptible to BD. According to the change in time course of TF and MCP-1 expression in the isolated islets, the selected time point for islet infusion in current clinical islet transplantation was thus shown to be at its worst level, at least with respect to the damage caused by BD and ischemic stress. In conclusion, BD in combination with warm ischemic stress during isolation procedures induces a high expression of TF and MCP-1 in the isolated islets. In order to reduce the expression of crucial inflammatory mediators in the islet grafts, the management of the pancreas from brain-dead donors with early anti-inflammatory treatments is thus warranted.https://doi.org/10.3727/096368910X508889
spellingShingle Yukihiko Saito
Masafumi Goto M.D., Ph.D.
Kozue Maya
Norihiko Ogawa
Keisei Fujimori
Yoshimochi Kurokawa
Susumu Satomi
Brain Death in Combination with Warm Ischemic Stress during Isolation Procedures Induces the Expression of Crucial Inflammatory Mediators in the Isolated Islets
Cell Transplantation
title Brain Death in Combination with Warm Ischemic Stress during Isolation Procedures Induces the Expression of Crucial Inflammatory Mediators in the Isolated Islets
title_full Brain Death in Combination with Warm Ischemic Stress during Isolation Procedures Induces the Expression of Crucial Inflammatory Mediators in the Isolated Islets
title_fullStr Brain Death in Combination with Warm Ischemic Stress during Isolation Procedures Induces the Expression of Crucial Inflammatory Mediators in the Isolated Islets
title_full_unstemmed Brain Death in Combination with Warm Ischemic Stress during Isolation Procedures Induces the Expression of Crucial Inflammatory Mediators in the Isolated Islets
title_short Brain Death in Combination with Warm Ischemic Stress during Isolation Procedures Induces the Expression of Crucial Inflammatory Mediators in the Isolated Islets
title_sort brain death in combination with warm ischemic stress during isolation procedures induces the expression of crucial inflammatory mediators in the isolated islets
url https://doi.org/10.3727/096368910X508889
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