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Cells
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Islet Transplantation
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Islet Transplantation

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

Deadline for manuscript submissions: closed (26 April 2024) | Viewed by 7497

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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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 (6 papers)

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Research

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16 pages, 5277 KiB  
Article
A Recombinant Peptide Device Combined with Adipose Tissue-Derived Stem Cells Enhances Subcutaneous Islet Engraftment
by Takahiro Mizui, Akiko Inagaki, Yasuhiro Nakamura, Takehiro Imura, Satomi Suzuki Uematsu, Shigehito Miyagi, Takashi Kamei, Michiaki Unno, Kimiko Watanabe and Masafumi Goto
Cells 2024, 13(6), 499; https://doi.org/10.3390/cells13060499 - 13 Mar 2024
Viewed by 776
Abstract
Subcutaneous space has been considered an attractive site for islet graft transplantation; however, the oxygen tension and vascularization are insufficient for islet graft survival. We investigated whether subcutaneous pre-implantation of a recombinant peptide (RCP) device with adipose tissue-derived stem cells (ADSCs) enhanced subcutaneous [...] Read more.
Subcutaneous space has been considered an attractive site for islet graft transplantation; however, the oxygen tension and vascularization are insufficient for islet graft survival. We investigated whether subcutaneous pre-implantation of a recombinant peptide (RCP) device with adipose tissue-derived stem cells (ADSCs) enhanced subcutaneous islet engraftment. RCP devices with/without syngeneic ADSCs were pre-implanted into the subcutaneous space of C57BL/6 mice. Syngeneic islets (300 or 120 islet equivalents (IEQs)) were transplanted into the pre-treated space after diabetes induction using streptozotocin. The cure rates of groups in which RCP devices were implanted four weeks before transplantation were significantly better than the intraportal transplantation group when 300 IEQs of islets were transplanted (p < 0.01). The blood glucose changes in the RCP+ADSCs-4w group was significantly ameliorated in comparison to the RCP-4w group when 120 IEQs of islets were transplanted (p < 0.01). Immunohistochemical analyses showed the collagen III expression in the islet capsule of the RCP+ADSCs-4w group was significantly enhanced in comparison to the RCP-4w and RCP+ADSCs-d10 groups (p < 0.01, p < 0.01). In addition, the number of von Willebrand factor-positive vessels within islets in the RCP+ADSCs-4w group was significantly higher than the RCP-4w group. These results suggest that using ADSCs in combination with an RCP device could enhance the restoration of the extracellular matrices, induce more efficient prevascularization within islets, and improve the graft function. Full article
(This article belongs to the Special Issue Islet Transplantation)
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15 pages, 2206 KiB  
Article
Inhibition of Toll-like Receptor 4 Using Small Molecule, TAK-242, Protects Islets from Innate Immune Responses
by Jordan Mattke, Carly M. Darden, Srividya Vasu, Michael C. Lawrence, Jeffrey Kirkland, Robert R. Kane and Bashoo Naziruddin
Cells 2024, 13(5), 416; https://doi.org/10.3390/cells13050416 - 27 Feb 2024
Viewed by 989
Abstract
Islet transplantation is a therapeutic option to replace β-cell mass lost during type 1 or type 3c diabetes. Innate immune responses, particularly the instant blood-mediated inflammatory reaction and activation of monocytes, play a major role in the loss of transplanted islet tissue. In [...] Read more.
Islet transplantation is a therapeutic option to replace β-cell mass lost during type 1 or type 3c diabetes. Innate immune responses, particularly the instant blood-mediated inflammatory reaction and activation of monocytes, play a major role in the loss of transplanted islet tissue. In this study, we aimed to investigate the inhibition of toll-like receptor 4 (TLR4) on innate inflammatory responses. We first demonstrate a significant loss of graft function shortly after transplant through the assessment of miR-375 and miR-200c in plasma as biomarkers. Using in vitro models, we investigate how targeting TLR4 mitigates islet damage and immune cell activation during the peritransplant period. The results of this study support the application of TAK-242 as a therapeutic agent to reduce inflammatory and innate immune responses to islets immediately following transplantation into the hepatic portal vein. Therefore, TLR4 may serve as a target to improve islet transplant outcomes in the future. Full article
(This article belongs to the Special Issue Islet Transplantation)
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14 pages, 3901 KiB  
Article
A Gelatin Hydrogel Nonwoven Fabric Enhances Subcutaneous Islet Engraftment in Rats
by 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 and Masafumi Goto
Cells 2024, 13(1), 51; https://doi.org/10.3390/cells13010051 - 26 Dec 2023
Viewed by 814
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
by Selina Wrublewsky, Cedric Wilden, Caroline Bickelmann, Michael D. Menger, Matthias W. Laschke and Emmanuel Ampofo
Cells 2024, 13(1), 16; https://doi.org/10.3390/cells13010016 (registering DOI) - 20 Dec 2023
Viewed by 834
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
by Jared M. Campbell, Stacey N. Walters, Abbas Habibalahi, Saabah B. Mahbub, Ayad G. Anwer, Shannon Handley, Shane T. Grey and Ewa M. Goldys
Cells 2023, 12(18), 2302; https://doi.org/10.3390/cells12182302 - 19 Sep 2023
Viewed by 1196
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
by Zofia Czarnecka, Nidheesh Dadheech, Haide Razavy, Rena Pawlick and A. M. James Shapiro
Cells 2023, 12(20), 2423; https://doi.org/10.3390/cells12202423 - 10 Oct 2023
Cited by 2 | Viewed by 2181
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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