A gelatin hydrogel nonwoven fabric improves outcomes of subcutaneous islet transplantation

Abstract Subcutaneous islet transplantation is a promising treatment for severe diabetes; however, poor engraftment hinders its prevalence. We previously reported that a recombinant peptide (RCP) enhances subcutaneous islet engraftment. However, it is impractical for clinical use because RCP must be...

Full description

Bibliographic Details
Main Authors: Norifumi Kanai, Akiko Inagaki, Yasuhiro Nakamura, Takehiro Imura, Hiroaki Mitsugashira, Ryusuke Saito, Shigehito Miyagi, Kimiko Watanabe, Takashi Kamei, Michiaki Unno, Yasuhiko Tabata, Masafumi Goto
Format: Article
Language:English
Published: Nature Portfolio 2023-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-39212-4
_version_ 1797769607660961792
author Norifumi Kanai
Akiko Inagaki
Yasuhiro Nakamura
Takehiro Imura
Hiroaki Mitsugashira
Ryusuke Saito
Shigehito Miyagi
Kimiko Watanabe
Takashi Kamei
Michiaki Unno
Yasuhiko Tabata
Masafumi Goto
author_facet Norifumi Kanai
Akiko Inagaki
Yasuhiro Nakamura
Takehiro Imura
Hiroaki Mitsugashira
Ryusuke Saito
Shigehito Miyagi
Kimiko Watanabe
Takashi Kamei
Michiaki Unno
Yasuhiko Tabata
Masafumi Goto
author_sort Norifumi Kanai
collection DOAJ
description Abstract Subcutaneous islet transplantation is a promising treatment for severe diabetes; however, poor engraftment hinders its prevalence. We previously reported that a recombinant peptide (RCP) enhances subcutaneous islet engraftment. However, it is impractical for clinical use because RCP must be removed when transplanting islets. We herein investigated whether a novel bioabsorbable gelatin hydrogel nonwoven fabric (GHNF) could improve subcutaneous islet engraftment. A silicon spacer with or without GHNF was implanted into the subcutaneous space of diabetic mice. Syngeneic islets were transplanted into the pretreated space or intraportally (Ipo group). Blood glucose, intraperitoneal glucose tolerance, immunohistochemistry, CT angiography and gene expression were evaluated. The cure rate and glucose tolerance of the GHNF group were significantly better than in the control and Ipo groups (p < 0.01, p < 0.05, respectively). In the GHNF group, a limited increase of vWF-positive vessels was detected in the islet capsule, whereas laminin (p < 0.05), collagen III and IV were considerably enhanced. TaqMan arrays revealed a significant upregulation of 19 target genes (including insulin-like growth factor-2) in the pretreated space. GHNF markedly improved the subcutaneous islet transplantation outcomes, likely due to ECM compensation and protection of islet function by various growth factors, rather than enhanced neovascularization.
first_indexed 2024-03-12T21:10:27Z
format Article
id doaj.art-e6628cebd77a4e26bd5fd1d7e4df1d27
institution Directory Open Access Journal
issn 2045-2322
language English
last_indexed 2024-03-12T21:10:27Z
publishDate 2023-07-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj.art-e6628cebd77a4e26bd5fd1d7e4df1d272023-07-30T11:12:34ZengNature PortfolioScientific Reports2045-23222023-07-0113111210.1038/s41598-023-39212-4A gelatin hydrogel nonwoven fabric improves outcomes of subcutaneous islet transplantationNorifumi Kanai0Akiko Inagaki1Yasuhiro Nakamura2Takehiro Imura3Hiroaki Mitsugashira4Ryusuke Saito5Shigehito Miyagi6Kimiko Watanabe7Takashi Kamei8Michiaki Unno9Yasuhiko Tabata10Masafumi Goto11Department of Surgery, Tohoku University Graduate School of MedicineDivision of Transplantation and Regenerative Medicine, Tohoku University Graduate School of MedicineDivision of Pathology, Graduate School of Medicine, Tohoku Medical and Pharmaceutical UniversityDivision of Transplantation and Regenerative Medicine, Tohoku University Graduate School of MedicineDepartment of Surgery, Tohoku University Graduate School of MedicineDepartment of Surgery, Tohoku University Graduate School of MedicineDepartment of Surgery, Tohoku University Graduate School of MedicineDivision of Transplantation and Regenerative Medicine, Tohoku University Graduate School of MedicineDepartment of Surgery, Tohoku University Graduate School of MedicineDepartment of Surgery, Tohoku University Graduate School of MedicineLaboratory of Biomaterials, Department of Regeneration Science and Engineering, Institute for Life and Medical Sciences (LiMe), Kyoto UniversityDepartment of Surgery, Tohoku University Graduate School of MedicineAbstract Subcutaneous islet transplantation is a promising treatment for severe diabetes; however, poor engraftment hinders its prevalence. We previously reported that a recombinant peptide (RCP) enhances subcutaneous islet engraftment. However, it is impractical for clinical use because RCP must be removed when transplanting islets. We herein investigated whether a novel bioabsorbable gelatin hydrogel nonwoven fabric (GHNF) could improve subcutaneous islet engraftment. A silicon spacer with or without GHNF was implanted into the subcutaneous space of diabetic mice. Syngeneic islets were transplanted into the pretreated space or intraportally (Ipo group). Blood glucose, intraperitoneal glucose tolerance, immunohistochemistry, CT angiography and gene expression were evaluated. The cure rate and glucose tolerance of the GHNF group were significantly better than in the control and Ipo groups (p < 0.01, p < 0.05, respectively). In the GHNF group, a limited increase of vWF-positive vessels was detected in the islet capsule, whereas laminin (p < 0.05), collagen III and IV were considerably enhanced. TaqMan arrays revealed a significant upregulation of 19 target genes (including insulin-like growth factor-2) in the pretreated space. GHNF markedly improved the subcutaneous islet transplantation outcomes, likely due to ECM compensation and protection of islet function by various growth factors, rather than enhanced neovascularization.https://doi.org/10.1038/s41598-023-39212-4
spellingShingle Norifumi Kanai
Akiko Inagaki
Yasuhiro Nakamura
Takehiro Imura
Hiroaki Mitsugashira
Ryusuke Saito
Shigehito Miyagi
Kimiko Watanabe
Takashi Kamei
Michiaki Unno
Yasuhiko Tabata
Masafumi Goto
A gelatin hydrogel nonwoven fabric improves outcomes of subcutaneous islet transplantation
Scientific Reports
title A gelatin hydrogel nonwoven fabric improves outcomes of subcutaneous islet transplantation
title_full A gelatin hydrogel nonwoven fabric improves outcomes of subcutaneous islet transplantation
title_fullStr A gelatin hydrogel nonwoven fabric improves outcomes of subcutaneous islet transplantation
title_full_unstemmed A gelatin hydrogel nonwoven fabric improves outcomes of subcutaneous islet transplantation
title_short A gelatin hydrogel nonwoven fabric improves outcomes of subcutaneous islet transplantation
title_sort gelatin hydrogel nonwoven fabric improves outcomes of subcutaneous islet transplantation
url https://doi.org/10.1038/s41598-023-39212-4
work_keys_str_mv AT norifumikanai agelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT akikoinagaki agelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT yasuhironakamura agelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT takehiroimura agelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT hiroakimitsugashira agelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT ryusukesaito agelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT shigehitomiyagi agelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT kimikowatanabe agelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT takashikamei agelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT michiakiunno agelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT yasuhikotabata agelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT masafumigoto agelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT norifumikanai gelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT akikoinagaki gelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT yasuhironakamura gelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT takehiroimura gelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT hiroakimitsugashira gelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT ryusukesaito gelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT shigehitomiyagi gelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT kimikowatanabe gelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT takashikamei gelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT michiakiunno gelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT yasuhikotabata gelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation
AT masafumigoto gelatinhydrogelnonwovenfabricimprovesoutcomesofsubcutaneousislettransplantation