Diabetes Metab J.
2026 May;50(3):495-505. 10.4093/dmj.2024.0400.
Pancreatic Islet Transplantation in Extrahepatic Sites: Evaluation of the Venous Sac in Large Mammal Models
- Kenchadze G
1 - Abiatari I1
- Pileggi A2,3,4,5
- Kenyon NS2,3
- Berman DM2,3
- Molano RD2
- Gogichaishvili K1
- Otarashvili R1
- Tchavtchavadze A1
- Midelashvili T1
- Motsikulashvili M1
- Ricordi C2,3
- Berney T1,6,7,8
- Berishvili E1,6,7,9
- Affiliations
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- 1Institute of Medical & Public Health Research, Ilia State University, Tbilisi, Georgia
- 2Cell Transplant Center, Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL, USA
- 3Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
- 4Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, FL, USA
- 5Department of Biomedical Engineering, University of Miami, FL, USA
- 6Cell Isolation and Transplantation Center, Department of Surgery, University of Geneva Hospitals, Geneva, Switzerland
- 7Faculty Diabetes Center, University of Geneva, Geneva, Switzerland
- 8Division of Transplantation, Nephrology and Clinical Immunology, Hospices Civils de Lyon, Lyon, France
- 9Tissue Engineering and Organ Regeneration Lab, Department of Surgery, University of Geneva, Geneva, Switzerland
- KMID: 2580522
- DOI: http://doi.org/10.4093/dmj.2024.0400
Abstract
- 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.
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