A novel subcutaneous islet transplantation method using a bioabsorbable medical device to facilitate the creation of a highly vascularized transplantation site

Subcutaneous transplantation is garnering attention as a potential transplantation site for pluripotent stem cell–derived islet cells to address the shortage of pancreatic islet transplant donors. However, subcutaneous transplantation of cells presents challenges related to angiogenesis, which is ne...

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Main Authors: Norio Emoto, Takayuki Anazawa, Kei Yamane, Nanae Fujimoto, Takaaki Murakami, Hiroyuki Fujimoto, Cui Jialin, Satoshi Ishida, Kouki Kurahashi, Aya Izuwa, Hang Su, Kenta Inoguchi, Seiichiro Tada, Kazuyuki Nagai, Etsuro Hatano
Format: Article
Language:English
Published: SAGE Publishing 2025-06-01
Series:Cell Transplantation
Online Access:https://doi.org/10.1177/09636897251342986
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author Norio Emoto
Takayuki Anazawa
Kei Yamane
Nanae Fujimoto
Takaaki Murakami
Hiroyuki Fujimoto
Cui Jialin
Satoshi Ishida
Kouki Kurahashi
Aya Izuwa
Hang Su
Kenta Inoguchi
Seiichiro Tada
Kazuyuki Nagai
Etsuro Hatano
author_facet Norio Emoto
Takayuki Anazawa
Kei Yamane
Nanae Fujimoto
Takaaki Murakami
Hiroyuki Fujimoto
Cui Jialin
Satoshi Ishida
Kouki Kurahashi
Aya Izuwa
Hang Su
Kenta Inoguchi
Seiichiro Tada
Kazuyuki Nagai
Etsuro Hatano
author_sort Norio Emoto
collection DOAJ
description Subcutaneous transplantation is garnering attention as a potential transplantation site for pluripotent stem cell–derived islet cells to address the shortage of pancreatic islet transplant donors. However, subcutaneous transplantation of cells presents challenges related to angiogenesis, which is necessary for successful islet bioproduction. This study aimed to investigate a novel method for enhancing vascularization at the transplant site and thereby promote islet engraftment using a clinically available bioabsorbable medical device. A nonabsorbable device (agarose) or a bioabsorbable device (collagen–gelatin sheet [CGS]) loaded with basic fibroblast growth factor (bFGF) was implanted subcutaneously in C57BL/6 mice. There were two other groups of mice, one of which was implanted with CGS alone, which acted as a control, and another group that was implanted with bFGF-loaded agarose rods. Subsequently, 200 islets were transplanted into the subcutaneous pre-vascularized sites. An equivalent number of islets was also transplanted into the portal vein (IPTx) to compare transplantation efficacy. Vascularization of the graft site was evaluated before and after transplantation. bFGF significantly enhanced angiogenesis in the CGS mice. The normalization rate of blood glucose levels following islet transplantation in the bFGF-loaded CGS was group comparable to that in the bFGF-loaded agarose rod and IPTx groups. The presence of islets was confirmed using single-photon emission computed tomography (SPECT/CT), histological examination. Furthermore, it was noted that blood glucose levels rapidly increased after graft removal, showing that graft function was crucial to maintain normoglycemia. Importantly, the bFGF-loaded CGS showed a high rate of engraftment. This novel bioabsorbable medical device method exhibited remarkable efficacy in enhancing subcutaneous islet engraftment, potentially paving the way for a more straightforward and less invasive approach for islet cell transplantation in future clinical applications.
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spelling doaj-art-78d7c831de1d47a49fb6abbafa185ae02025-08-20T02:06:23ZengSAGE PublishingCell Transplantation1555-38922025-06-013410.1177/09636897251342986A novel subcutaneous islet transplantation method using a bioabsorbable medical device to facilitate the creation of a highly vascularized transplantation siteNorio Emoto0Takayuki Anazawa1Kei Yamane2Nanae Fujimoto3Takaaki Murakami4Hiroyuki Fujimoto5Cui Jialin6Satoshi Ishida7Kouki Kurahashi8Aya Izuwa9Hang Su10Kenta Inoguchi11Seiichiro Tada12Kazuyuki Nagai13Etsuro Hatano14Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDivision of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDivision of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanInstitute for Life and Medical Sciences, Department of Regeneration Science and Engineering, Kyoto University, Kyoto, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanRadioisotope Research Center, Agency for Health, Safety and Environment, Kyoto University, Kyoto, JapanDivision of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDivision of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDivision of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDivision of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDivision of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDivision of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDivision of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDivision of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDivision of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanSubcutaneous transplantation is garnering attention as a potential transplantation site for pluripotent stem cell–derived islet cells to address the shortage of pancreatic islet transplant donors. However, subcutaneous transplantation of cells presents challenges related to angiogenesis, which is necessary for successful islet bioproduction. This study aimed to investigate a novel method for enhancing vascularization at the transplant site and thereby promote islet engraftment using a clinically available bioabsorbable medical device. A nonabsorbable device (agarose) or a bioabsorbable device (collagen–gelatin sheet [CGS]) loaded with basic fibroblast growth factor (bFGF) was implanted subcutaneously in C57BL/6 mice. There were two other groups of mice, one of which was implanted with CGS alone, which acted as a control, and another group that was implanted with bFGF-loaded agarose rods. Subsequently, 200 islets were transplanted into the subcutaneous pre-vascularized sites. An equivalent number of islets was also transplanted into the portal vein (IPTx) to compare transplantation efficacy. Vascularization of the graft site was evaluated before and after transplantation. bFGF significantly enhanced angiogenesis in the CGS mice. The normalization rate of blood glucose levels following islet transplantation in the bFGF-loaded CGS was group comparable to that in the bFGF-loaded agarose rod and IPTx groups. The presence of islets was confirmed using single-photon emission computed tomography (SPECT/CT), histological examination. Furthermore, it was noted that blood glucose levels rapidly increased after graft removal, showing that graft function was crucial to maintain normoglycemia. Importantly, the bFGF-loaded CGS showed a high rate of engraftment. This novel bioabsorbable medical device method exhibited remarkable efficacy in enhancing subcutaneous islet engraftment, potentially paving the way for a more straightforward and less invasive approach for islet cell transplantation in future clinical applications.https://doi.org/10.1177/09636897251342986
spellingShingle Norio Emoto
Takayuki Anazawa
Kei Yamane
Nanae Fujimoto
Takaaki Murakami
Hiroyuki Fujimoto
Cui Jialin
Satoshi Ishida
Kouki Kurahashi
Aya Izuwa
Hang Su
Kenta Inoguchi
Seiichiro Tada
Kazuyuki Nagai
Etsuro Hatano
A novel subcutaneous islet transplantation method using a bioabsorbable medical device to facilitate the creation of a highly vascularized transplantation site
Cell Transplantation
title A novel subcutaneous islet transplantation method using a bioabsorbable medical device to facilitate the creation of a highly vascularized transplantation site
title_full A novel subcutaneous islet transplantation method using a bioabsorbable medical device to facilitate the creation of a highly vascularized transplantation site
title_fullStr A novel subcutaneous islet transplantation method using a bioabsorbable medical device to facilitate the creation of a highly vascularized transplantation site
title_full_unstemmed A novel subcutaneous islet transplantation method using a bioabsorbable medical device to facilitate the creation of a highly vascularized transplantation site
title_short A novel subcutaneous islet transplantation method using a bioabsorbable medical device to facilitate the creation of a highly vascularized transplantation site
title_sort novel subcutaneous islet transplantation method using a bioabsorbable medical device to facilitate the creation of a highly vascularized transplantation site
url https://doi.org/10.1177/09636897251342986
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