Functional maturation and longitudinal imaging of intraportal neonatal porcine islet grafts in genetically diabetic pigs

Pilz, Johanna ; Gloddek, Nicol ; Lindheimer, Felix ; Lindner, Magdalena Julia; Puhr-Westerheide, Daniel ; Ümütlü, Muzzafer; Cyran, Clemens ; Seidensticker, Max ; Lindner, Richard ; Kraetzl, Martin ; Renner, Simone ; Merkus, Daphne ; Teupser, Daniel ; Bartenstein, Peter ; Ziegler, Sibylle I. ; Wolf, Eckhard und Kemter, Elisabeth (2024): Functional maturation and longitudinal imaging of intraportal neonatal porcine islet grafts in genetically diabetic pigs. In: American Journal of Transplantation, Bd. 24, Nr. 8: S. 1395-1405

Abstract

Allogeneic intraportal islet transplantation (ITx) has become an established treatment for patients with poorly controlled type 1 diabetes. However, the loss of viable beta-cell mass after transplantation remains a major challenge. Therefore, noninvasive imaging methods for long-term monitoring of the transplant fate are required. In this study, [68Ga]Ga-DOTA-exendin-4 positron emission tomography/computed tomography (PET/CT) was used for repeated monitoring of allogeneic neonatal porcine islets (NPI) after intraportal transplantation into immunosuppressed genetically diabetic pigs. NPI transplantation (3320-15,000 islet equivalents per kg body weight) led to a reduced need for exogenous insulin therapy and finally normalization of blood glucose levels in 3 out of 4 animals after 5 to 10 weeks. Longitudinal PET/CT measurements revealed a significant increase in standard uptake values in graft-bearing livers. Histologic analysis confirmed the presence of well-engrafted, mature islet clusters in the transplanted livers. Our study presents a novel large animal model for allogeneic intraportal ITx. A relatively small dose of NPIs was sufficient to normalize blood glucose levels in a clinically relevant diabetic pig model. [68Ga]Ga-DOTA-exendin-4 PET/CT proved to be efficacious for longitudinal monitoring of islet transplants. Thus, it could play a crucial role in optimizing ITx as a curative therapy for type 1 diabetes.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Tiermedizin > Veterinärwissenschaftliches Department > Lehrstuhl für Molekulare Tierzucht und Biotechnologie ; Medizin > Klinikum der LMU München > Klinik für Allgemeine, Viszeral-, Gefäß- und Transplantationschirurgie ; Medizin > Klinikum der LMU München > Klinik und Poliklinik für Nuklearmedizin ; Medizin > Klinikum der LMU München > Klinik und Poliklinik für Radiologie ; Medizin > Klinikum der LMU München > Institut für Laboratoriumsmedizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 16006135
• Sprache: Englisch