Reestablishment of Microenvironment is Necessary to Maintain In Vitro and In Vivo Human Islet Function
Islet transplantation is associated with an elevated rate of early graft failure. The isolation process leads to structural and functional abnormalities. The reestablishment of the cell–matrix relationship is important to modulate the survival and function of islets. Thus, we evaluated the effect of...
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doaj-5e6614bbac4b40e1a0ee8c419aa69bd92020-11-25T03:07:36ZengSAGE PublishingCell Transplantation0963-68971555-38922008-01-011710.3727/000000008783907125Reestablishment of Microenvironment is Necessary to Maintain In Vitro and In Vivo Human Islet FunctionNalú Navarro-Alvarez0Jorge David Rivas-Carrillo1Alejandro Soto-Gutierrez2Takeshi Yuasa3Teru Okitsu4Hirofumi Noguchi5Shinichi Matsumoto6Jiro Takei7Noriaki Tanaka8Naoya Kobayashi M.D., PH.D.9Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, JapanDepartment of Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, JapanDepartment of Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, JapanDepartment of Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, JapanDepartment of Transplant Medicine, Kyoto University Hospital, Kyoto 606-8507, JapanBaylor Institution for Immunology Research, Islet Cell Transplantation Laboratory, Baylor Research Institute, Dallas, TX 75204, USABaylor Institution for Immunology Research, Islet Cell Transplantation Laboratory, Baylor Research Institute, Dallas, TX 75204, USA3-DMatrix Japan, Ltd., Tokyo 102-0083, JapanDepartment of Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, JapanDepartment of Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, JapanIslet transplantation is associated with an elevated rate of early graft failure. The isolation process leads to structural and functional abnormalities. The reestablishment of the cell–matrix relationship is important to modulate the survival and function of islets. Thus, we evaluated the effect of human fibronectin (hFN) and self-assembling peptide nanofiber (SAPNF) in the ability to support islet function in vitro and after transplantation into streptozotocin (STZ)-induced diabetic severe combined immunodeficiency (SCID) mice. Human isolated islets were cultured with hFN or SAPNF for 7 days. Their ability to maintain insulin production/glucose responsiveness over time was evaluated. Islets embedded in hFN, SAPNF, or alone were transplanted into STZ-induced diabetic SCID mice. Islet grafts were removed after 14 days to evaluate insulin content, insulin expression, and apoptosis. SAPNF-entrapped islets maintained satisfactory morphology/viability and capability of glucose-dependent insulin secretion for over 7 days, whereas islets cultured in hFN underwent widespread deterioration. In vivo grafts containing human islets in SAPNF showed remarkably higher insulin content and expression when compared with human islets in hFn or alone. RT-PCR revealed lower caspase-3 expression in SAPNF islets grafts. These studies indicate that the reestablishment of the cell–matrix interactions by a synthetic matrix in the immediate postisolation period is a useful tool to maintain islet functions in vitro and in vivo.https://doi.org/10.3727/000000008783907125 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nalú Navarro-Alvarez Jorge David Rivas-Carrillo Alejandro Soto-Gutierrez Takeshi Yuasa Teru Okitsu Hirofumi Noguchi Shinichi Matsumoto Jiro Takei Noriaki Tanaka Naoya Kobayashi M.D., PH.D. |
spellingShingle |
Nalú Navarro-Alvarez Jorge David Rivas-Carrillo Alejandro Soto-Gutierrez Takeshi Yuasa Teru Okitsu Hirofumi Noguchi Shinichi Matsumoto Jiro Takei Noriaki Tanaka Naoya Kobayashi M.D., PH.D. Reestablishment of Microenvironment is Necessary to Maintain In Vitro and In Vivo Human Islet Function Cell Transplantation |
author_facet |
Nalú Navarro-Alvarez Jorge David Rivas-Carrillo Alejandro Soto-Gutierrez Takeshi Yuasa Teru Okitsu Hirofumi Noguchi Shinichi Matsumoto Jiro Takei Noriaki Tanaka Naoya Kobayashi M.D., PH.D. |
author_sort |
Nalú Navarro-Alvarez |
title |
Reestablishment of Microenvironment is Necessary to Maintain In Vitro and In Vivo Human Islet Function |
title_short |
Reestablishment of Microenvironment is Necessary to Maintain In Vitro and In Vivo Human Islet Function |
title_full |
Reestablishment of Microenvironment is Necessary to Maintain In Vitro and In Vivo Human Islet Function |
title_fullStr |
Reestablishment of Microenvironment is Necessary to Maintain In Vitro and In Vivo Human Islet Function |
title_full_unstemmed |
Reestablishment of Microenvironment is Necessary to Maintain In Vitro and In Vivo Human Islet Function |
title_sort |
reestablishment of microenvironment is necessary to maintain in vitro and in vivo human islet function |
publisher |
SAGE Publishing |
series |
Cell Transplantation |
issn |
0963-6897 1555-3892 |
publishDate |
2008-01-01 |
description |
Islet transplantation is associated with an elevated rate of early graft failure. The isolation process leads to structural and functional abnormalities. The reestablishment of the cell–matrix relationship is important to modulate the survival and function of islets. Thus, we evaluated the effect of human fibronectin (hFN) and self-assembling peptide nanofiber (SAPNF) in the ability to support islet function in vitro and after transplantation into streptozotocin (STZ)-induced diabetic severe combined immunodeficiency (SCID) mice. Human isolated islets were cultured with hFN or SAPNF for 7 days. Their ability to maintain insulin production/glucose responsiveness over time was evaluated. Islets embedded in hFN, SAPNF, or alone were transplanted into STZ-induced diabetic SCID mice. Islet grafts were removed after 14 days to evaluate insulin content, insulin expression, and apoptosis. SAPNF-entrapped islets maintained satisfactory morphology/viability and capability of glucose-dependent insulin secretion for over 7 days, whereas islets cultured in hFN underwent widespread deterioration. In vivo grafts containing human islets in SAPNF showed remarkably higher insulin content and expression when compared with human islets in hFn or alone. RT-PCR revealed lower caspase-3 expression in SAPNF islets grafts. These studies indicate that the reestablishment of the cell–matrix interactions by a synthetic matrix in the immediate postisolation period is a useful tool to maintain islet functions in vitro and in vivo. |
url |
https://doi.org/10.3727/000000008783907125 |
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