Diabetes & Metabolism Journal

Original Article

Basic and Translational Research
Pancreatic Islet Transplantation in Extrahepatic Sites: Evaluation of the Venous Sac in Large Mammal Models: Giorgi Kenchadze, Ivane Abiatari, Antonello Pileggi, Norma S. Kenyon, Dora M Berman, R. Damaris Molano, Konstantine Gogichaishvili, Revaz Otarashvili, Anzor Tchavtchavadze, Teona Midelashvili, Mariam Motsikulashvili, Camillo Ricordi, Thierry Berney, Ekaterine Berishvili; Received July 19, 2024 Accepted April 28, 2025 Published online September 8, 2025; DOI: https://doi.org/10.4093/dmj.2024.0400 [Epub ahead of print]

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Abstract PDF PubReader ePub: Background
The long-term clinical efficacy of intraportal islet transplantation is hampered by islet loss due to inflammation, oxidative stress, and insufficient vascularization. This study explores the venous sac as an alternative implantation site for islet transplantation in large animal models.
Methods
An immunosuppressed, diabetic cynomolgus monkey received allogeneic islet implants in its mesenteric venous sac, with metabolic assessments over 112 days. Dogs underwent islet autotransplantation into various venous sacs, with their glycemic control and other metabolic parameters monitored for 1 month.
Results
In an nonhuman primate, the mesenteric venous sac site improved glycemic control over a 3-month period, followed by destabilization of graft function. Histologic studies revealed healthy islets. The lack of mononuclear cell infiltrate suggested no signs of graft rejection. Saphenous venous sacs in dogs showed superior glycemic control, reduced insulin requirements, and maintained C-peptide levels, comparable to intraportal transplantation. Histological analyses confirmed islet preservation and graft vascularization in saphenous venous sacs.
Conclusion
This study provides preclinical evidence in support of the venous sac as a valuable extrahepatic location for pancreatic islet implantation. We found that the saphenous vein is a more effective site for islet engraftment than the mesenteric vein. This study offers potential benefits for improving the success rates of clinical islet transplantation.

Short Communication

Islet Studies and Transplantation
Alginate-Catechol Cross-Linking Interferes with Insulin Secretion Capacity in Isolated Murine Islet Cells: Yu-Sik Kim, Seung-Woo Cho, Bomin Ko, Jisoo Shin, Chul Woo Ahn; Diabetes Metab J. 2018;42(2):164-168. Published online March 28, 2018; DOI: https://doi.org/10.4093/dmj.2018.42.2.164

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6 Web of Science
6 Crossref

Over the past three decades, human pancreatic islet isolation and transplantation techniques have developed as a routine clinical procedure for selected patients with type 1 diabetes mellitus. However, due to the donor shortage and required chronic systemic immunosuppression, the widespread application of islet transplantation is limited. To overcome these limitations, providing a physical barrier to transplanted islet cells with encapsulating biomaterial has emerged as a promising approach to enhance engraftment and promote islet survival post-transplantation. Alginate has been considered to be a reliable biomaterial, as it enhances islet survival and does not hamper hormone secretion. Alginate-catechol (Al-CA) hydrogel was reported to provide high mechanical strength and chemical stability without deformation over a wide range of pH values. In this study, we, demonstrated, for the first time in the literature, that encapsulation of murine pancreatic islet cells with Al-CA hydrogel does not induce cytotoxicity ex vivo for an extended period; however, it does markedly abate glucose-stimulated insulin secretion. Catechol should not be considered as a constituent for alginate gelation for encapsulating islet cells in the application of islet transplantation.

Citations

Citations to this article as recorded by

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Polymer Science, Series B.2021; 63(6): 640. CrossRef
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AAPS PharmSciTech.2020;[Epub] CrossRef

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