C-Peptide Determinations in Islet Xenotransplantation: A Study in the Pig-to-Mouse Model

• Published in: Cell transplantation 2001-03, Vol.10 (2), p.165-173
• Main Authors: Wennberg, L., Sundberg, B., Ekdahl-Nilsson, K., Korsgren, O.
• Format: Article
• Language: English
• Subjects: Animals; C-Peptide - blood; C-Peptide - pharmacokinetics; C-Peptide - urine; Cell Culture Techniques - methods; Cells, Cultured; Diabetes Mellitus, Experimental - surgery; Fetal Tissue Transplantation - physiology; Glycosylation; Iodine Radioisotopes - pharmacokinetics; Islets of Langerhans - cytology; Islets of Langerhans - embryology; Islets of Langerhans Transplantation - physiology; Medicin och hälsovetenskap; Mice; Mice, Inbred BALB C; Mice, Inbred Strains; Mice, Nude; Subrenal Capsule Assay; Swine; Tissue Distribution; Transplantation, Heterologous - physiology
• ISSN: 0963-6897; 1555-3892
• DOI: 10.3727/000000001783986918

Assays of C-peptide are used to monitor allogeneic islet graft function. However, it is not known whether xenogeneic C-peptide is metabolized and excreted in a fashion similar to endogenous and allogeneic C-peptide. In this study, injection of 10 times the physiological amount of porcine C-peptide into mice did not result in the excretion of the C-peptide in the urine. In contrast, when a physiological amount of porcine C-peptide was injected into athymic mice, urinary excretion of porcine C-peptide was readily detected. After injection of radioactively labeled porcine C-peptide into mice, the radioactive uptake in tissues belonging to the mononuclear phagocytic system was significantly increased in mice immunized towards the xenogeneic C-peptide. These results may reflect an immunological reactivity towards the C-peptide. Antibodies against porcine C-peptide could not be detected in the serum of any of the mice. However, porcine C-peptide was found to be glycosylated. Thus, a possible explanation to the lack of porcine C-peptide in the urine is that xenoreactive antibodies had bound to carbohydrate structures on the peptide and that the antibody – C-peptide complex had been cleared from the circulation by the mononuclear phagocytic system. Thus, the urinary excretion of xenogeneic C-peptide seems to be different from that of endogenous and allogeneic C-peptide. Consequently, determinations of donor-specific C-peptide may not properly reflect islet xenograft function. In fact, islet xenograft function may be underestimated.