Islet Transplantation

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 26 April 2024 | Viewed by 4174

Special Issue Editor

Dr. Shinichi Matsumoto
E-Mail Website
Guest Editor
National Center for Global Health and Medicine, Tokyo, Japan
Interests: allogeneic islet transplantation; autologous islet transplantation; xenogeneic islet transplantation; regenerative medicine to treat diabetes

Special Issue Information

Dear Colleagues,

To date, diabetes is an incurable disease; however, beta cell replacement therapy can be a curative treatment for the diabetes.

Among the beta cell replacement therapies, islet transplantation has been evolutionally developed.

Allogenic islet transplantation has become the standard therapy for the treatment of type 1 diabetes, and, in some countries, autologous islet transplantation with total pancreatectomy has also become the standard therapy for the treatment of painful chronic pancreatitis.

Xenogeneic islet transplantation and regenerative medicine using stem cells for the treatment of diabetes is now entering the clinical trial phase.

Islet transplantation has been leading in the field of cell therapy and the progress being currently obtained is considerably exciting.

This Special Issue aims to explore the current state of the art of islet transplantation and future research focuses within this area.

Dr. Shinichi Matsumoto
Guest Editor

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Keywords

  • allogeneic islet transplantation
  • islet isolation
  • immunosuppression for islet transplantation
  • autologous islet transplantation
  • xenogeneic islet transplantation
  • transplantation site for islet transplantation
  • regenerative medicine for the treatment of diabetes

Published Papers (4 papers)

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Research

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14 pages, 3901 KiB  
Article
A Gelatin Hydrogel Nonwoven Fabric Enhances Subcutaneous Islet Engraftment in Rats
Cells 2024, 13(1), 51; https://doi.org/10.3390/cells13010051 - 26 Dec 2023
Viewed by 561
Abstract
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 [...] Read more.
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 (p < 0.01). The cure rate was significantly higher in the GHNF group (p < 0.05). The number of vWF-positive vessels was significantly higher in the GHNF group (p < 0.01), and lectin angiography showed the same tendency (p < 0.05). The expression of laminin and collagen III around the transplanted islets was also higher in the GHNF group (p < 0.01). GHNF pretreatment was effective in a rat model, and the main mechanisms might be neovascularization and compensation of the extracellular matrices. Full article
(This article belongs to the Special Issue Islet Transplantation)
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15 pages, 2503 KiB  
Article
Absent in Melanoma (AIM)2 Promotes the Outcome of Islet Transplantation by Repressing Ischemia-Induced Interferon (IFN) Signaling
Cells 2024, 13(1), 16; https://doi.org/10.3390/cells13010016 (registering DOI) - 20 Dec 2023
Viewed by 601
Abstract
Clinical islet transplantation is limited by ischemia-induced islet cell death. Recently, it has been reported that the absent in melanoma (AIM)2 inflammasome is upregulated by ischemic cell death due to recognition of aberrant cytoplasmic self-dsDNA. However, it is unknown whether AIM2 determines the [...] Read more.
Clinical islet transplantation is limited by ischemia-induced islet cell death. Recently, it has been reported that the absent in melanoma (AIM)2 inflammasome is upregulated by ischemic cell death due to recognition of aberrant cytoplasmic self-dsDNA. However, it is unknown whether AIM2 determines the outcome of islet transplantation. To investigate this, isolated wild type (WT) and AIM2-deficient (AIM2−/−) islets were exposed to oxygen-glucose deprivation to mimic ischemia, and their viability, endocrine function, and interferon (IFN) signaling were assessed. Moreover, the revascularization and endocrine function of grafted WT and AIM2−/− islets were analyzed in the mouse dorsal skinfold chamber model and the diabetic kidney capsule model. Ischemic WT and AIM2−/− islets did not differ in their viability. However, AIM2−/− islets exhibited a higher protein level of p202, a transcriptional regulator of IFN-β and IFN-γ gene expression. Accordingly, these cytokines were upregulated in AIM2−/− islets, resulting in a suppressed gene expression and secretion of insulin. Moreover, the revascularization of AIM2−/− islet grafts was deteriorated when compared to WT controls. Furthermore, transplantation of AIM2−/− islets in diabetic mice failed to restore physiological blood glucose levels. These findings indicate that AIM2 crucially determines the engraftment and endocrine function of transplanted islets by repressing IFN signaling. Full article
(This article belongs to the Special Issue Islet Transplantation)
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19 pages, 13972 KiB  
Article
Pancreatic Islet Viability Assessment Using Hyperspectral Imaging of Autofluorescence
Cells 2023, 12(18), 2302; https://doi.org/10.3390/cells12182302 - 19 Sep 2023
Viewed by 999
Abstract
Islets prepared for transplantation into type 1 diabetes patients are exposed to compromising intrinsic and extrinsic factors that contribute to early graft failure, necessitating repeated islet infusions for clinical insulin independence. A lack of reliable pre-transplant measures to determine islet viability severely limits [...] Read more.
Islets prepared for transplantation into type 1 diabetes patients are exposed to compromising intrinsic and extrinsic factors that contribute to early graft failure, necessitating repeated islet infusions for clinical insulin independence. A lack of reliable pre-transplant measures to determine islet viability severely limits the success of islet transplantation and will limit future beta cell replacement strategies. We applied hyperspectral fluorescent microscopy to determine whether we could non-invasively detect islet damage induced by oxidative stress, hypoxia, cytokine injury, and warm ischaemia, and so predict transplant outcomes in a mouse model. In assessing islet spectral signals for NAD(P)H, flavins, collagen-I, and cytochrome-C in intact islets, we distinguished islets compromised by oxidative stress (ROS) (AUC = 1.00), hypoxia (AUC = 0.69), cytokine exposure (AUC = 0.94), and warm ischaemia (AUC = 0.94) compared to islets harvested from pristine anaesthetised heart-beating mouse donors. Significantly, with unsupervised assessment we defined an autofluorescent score for ischaemic islets that accurately predicted the restoration of glucose control in diabetic recipients following transplantation. Similar results were obtained for islet single cell suspensions, suggesting translational utility in the context of emerging beta cell replacement strategies. These data show that the pre-transplant hyperspectral imaging of islet autofluorescence has promise for predicting islet viability and transplant success. Full article
(This article belongs to the Special Issue Islet Transplantation)
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Review

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13 pages, 2172 KiB  
Review
The Current Status of Allogenic Islet Cell Transplantation
Cells 2023, 12(20), 2423; https://doi.org/10.3390/cells12202423 - 10 Oct 2023
Cited by 2 | Viewed by 1486
Abstract
Type 1 Diabetes (T1D) is an autoimmune destruction of pancreatic beta cells. The development of the Edmonton Protocol for islet transplantation in 2000 revolutionized T1D treatment and offered a glimpse at a cure for the disease. In 2022, the 20-year follow-up findings of [...] Read more.
Type 1 Diabetes (T1D) is an autoimmune destruction of pancreatic beta cells. The development of the Edmonton Protocol for islet transplantation in 2000 revolutionized T1D treatment and offered a glimpse at a cure for the disease. In 2022, the 20-year follow-up findings of islet cell transplantation demonstrated the long-term safety of islet cell transplantation despite chronic immunosuppression. The Edmonton Protocol, however, remains limited by two obstacles: scarce organ donor availability and risks associated with chronic immunosuppression. To overcome these challenges, the search has begun for an alternative cell source. In 2006, pluripotency genomic factors, coined “Yamanaka Factors,” were discovered, which reprogram mature somatic cells back to their embryonic, pluripotent form (iPSC). iPSCs can then be differentiated into specialized cell types, including islet cells. This discovery has opened a gateway to a personalized medicine approach to treating diabetes, circumventing the issues of donor supply and immunosuppression. In this review, we present a brief history of allogenic islet cell transplantation from the early days of pancreatic remnant transplantation to present work on encapsulating stem cell-derived cells. We review data on long-term outcomes and the ongoing challenges of allogenic islet cell and stem cell-derived islet cell transplant. Full article
(This article belongs to the Special Issue Islet Transplantation)
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