A Gelatin Hydrogel Nonwoven Fabric Enhances Subcutaneous Islet Engraftment in Rats

Although subcutaneous islet transplantation has many advantages, the subcutaneous space is poor in vessels and transplant efficiency is still low in animal models, except in mice. Subcutaneous islet transplantation using a two-step approach has been proposed, in which a favorable cavity is first pre...

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Main Authors: Ryusuke Saito, Akiko Inagaki, Yasuhiro Nakamura, Takehiro Imura, Norifumi Kanai, Hiroaki Mitsugashira, Yukiko Endo Kumata, Takumi Katano, Shoki Suzuki, Kazuaki Tokodai, Takashi Kamei, Michiaki Unno, Kimiko Watanabe, Yasuhiko Tabata, Masafumi Goto
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/13/1/51
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author Ryusuke Saito
Akiko Inagaki
Yasuhiro Nakamura
Takehiro Imura
Norifumi Kanai
Hiroaki Mitsugashira
Yukiko Endo Kumata
Takumi Katano
Shoki Suzuki
Kazuaki Tokodai
Takashi Kamei
Michiaki Unno
Kimiko Watanabe
Yasuhiko Tabata
Masafumi Goto
author_facet Ryusuke Saito
Akiko Inagaki
Yasuhiro Nakamura
Takehiro Imura
Norifumi Kanai
Hiroaki Mitsugashira
Yukiko Endo Kumata
Takumi Katano
Shoki Suzuki
Kazuaki Tokodai
Takashi Kamei
Michiaki Unno
Kimiko Watanabe
Yasuhiko Tabata
Masafumi Goto
author_sort Ryusuke Saito
collection DOAJ
description Although subcutaneous islet transplantation has many advantages, the subcutaneous space is poor in vessels and transplant efficiency is still low in animal models, except in mice. Subcutaneous islet transplantation using a two-step approach has been proposed, in which a favorable cavity is first prepared using various materials, followed by islet transplantation into the preformed cavity. We previously reported the efficacy of pretreatment using gelatin hydrogel nonwoven fabric (GHNF), and the length of the pretreatment period influenced the results in a mouse model. We investigated whether the preimplantation of GHNF could improve the subcutaneous islet transplantation outcomes in a rat model. GHNF sheets sandwiching a silicone spacer (GHNF group) and silicone spacers without GHNF sheets (control group) were implanted into the subcutaneous space of recipients three weeks before islet transplantation, and diabetes was induced seven days before islet transplantation. Syngeneic islets were transplanted into the space where the silicone spacer was removed. Blood glucose levels, glucose tolerance, immunohistochemistry, and neovascularization were evaluated. The GHNF group showed significantly better blood glucose changes than the control group (<i>p</i> < 0.01). The cure rate was significantly higher in the GHNF group (<i>p</i> < 0.05). The number of vWF-positive vessels was significantly higher in the GHNF group (<i>p</i> < 0.01), and lectin angiography showed the same tendency (<i>p</i> < 0.05). The expression of laminin and collagen III around the transplanted islets was also higher in the GHNF group (<i>p</i> < 0.01). GHNF pretreatment was effective in a rat model, and the main mechanisms might be neovascularization and compensation of the extracellular matrices.
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spelling doaj.art-edd667a4dd4f440788620d9429cf27e82024-01-10T14:53:19ZengMDPI AGCells2073-44092023-12-011315110.3390/cells13010051A Gelatin Hydrogel Nonwoven Fabric Enhances Subcutaneous Islet Engraftment in RatsRyusuke Saito0Akiko Inagaki1Yasuhiro Nakamura2Takehiro Imura3Norifumi Kanai4Hiroaki Mitsugashira5Yukiko Endo Kumata6Takumi Katano7Shoki Suzuki8Kazuaki Tokodai9Takashi Kamei10Michiaki Unno11Kimiko Watanabe12Yasuhiko Tabata13Masafumi Goto14Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-0872, JapanDivision of Transplantation and Regenerative Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDivision of Pathology, Graduate School of Medicine, Tohoku Medical and Pharmaceutical University, Sendai 983-8536, JapanDivision of Transplantation and Regenerative Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDepartment of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-0872, JapanDepartment of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-0872, JapanDepartment of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-0872, JapanDivision of Transplantation and Regenerative Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDepartment of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-0872, JapanDepartment of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-0872, JapanDepartment of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-0872, JapanDepartment of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-0872, JapanDivision of Transplantation and Regenerative Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanLaboratory of Biomaterials, Department of Regeneration Science and Engineering, Institute for Life and Medical Sciences (LiMe), Kyoto University, Kyoto 606-8507, JapanDepartment of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-0872, JapanAlthough subcutaneous islet transplantation has many advantages, the subcutaneous space is poor in vessels and transplant efficiency is still low in animal models, except in mice. Subcutaneous islet transplantation using a two-step approach has been proposed, in which a favorable cavity is first prepared using various materials, followed by islet transplantation into the preformed cavity. We previously reported the efficacy of pretreatment using gelatin hydrogel nonwoven fabric (GHNF), and the length of the pretreatment period influenced the results in a mouse model. We investigated whether the preimplantation of GHNF could improve the subcutaneous islet transplantation outcomes in a rat model. GHNF sheets sandwiching a silicone spacer (GHNF group) and silicone spacers without GHNF sheets (control group) were implanted into the subcutaneous space of recipients three weeks before islet transplantation, and diabetes was induced seven days before islet transplantation. Syngeneic islets were transplanted into the space where the silicone spacer was removed. Blood glucose levels, glucose tolerance, immunohistochemistry, and neovascularization were evaluated. The GHNF group showed significantly better blood glucose changes than the control group (<i>p</i> < 0.01). The cure rate was significantly higher in the GHNF group (<i>p</i> < 0.05). The number of vWF-positive vessels was significantly higher in the GHNF group (<i>p</i> < 0.01), and lectin angiography showed the same tendency (<i>p</i> < 0.05). The expression of laminin and collagen III around the transplanted islets was also higher in the GHNF group (<i>p</i> < 0.01). GHNF pretreatment was effective in a rat model, and the main mechanisms might be neovascularization and compensation of the extracellular matrices.https://www.mdpi.com/2073-4409/13/1/51isletsgelatin hydrogel nonwoven fabricssubcutaneous transplantationextracellular matrixneovascularizationrats
spellingShingle Ryusuke Saito
Akiko Inagaki
Yasuhiro Nakamura
Takehiro Imura
Norifumi Kanai
Hiroaki Mitsugashira
Yukiko Endo Kumata
Takumi Katano
Shoki Suzuki
Kazuaki Tokodai
Takashi Kamei
Michiaki Unno
Kimiko Watanabe
Yasuhiko Tabata
Masafumi Goto
A Gelatin Hydrogel Nonwoven Fabric Enhances Subcutaneous Islet Engraftment in Rats
Cells
islets
gelatin hydrogel nonwoven fabrics
subcutaneous transplantation
extracellular matrix
neovascularization
rats
title A Gelatin Hydrogel Nonwoven Fabric Enhances Subcutaneous Islet Engraftment in Rats
title_full A Gelatin Hydrogel Nonwoven Fabric Enhances Subcutaneous Islet Engraftment in Rats
title_fullStr A Gelatin Hydrogel Nonwoven Fabric Enhances Subcutaneous Islet Engraftment in Rats
title_full_unstemmed A Gelatin Hydrogel Nonwoven Fabric Enhances Subcutaneous Islet Engraftment in Rats
title_short A Gelatin Hydrogel Nonwoven Fabric Enhances Subcutaneous Islet Engraftment in Rats
title_sort gelatin hydrogel nonwoven fabric enhances subcutaneous islet engraftment in rats
topic islets
gelatin hydrogel nonwoven fabrics
subcutaneous transplantation
extracellular matrix
neovascularization
rats
url https://www.mdpi.com/2073-4409/13/1/51
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