Intrahepatic islet transplant in the mouse: functional and morphological characterization

Area of Science:

• Immunology
• Transplantation Biology
• Diabetology

Background:

• Clinical islet transplantation typically uses intrahepatic infusion.
• Mouse studies predominantly use the kidney capsule site for islet transplantation.
• The intraportal vein infusion model in mice requires extensive characterization.

Purpose of the Study:

• To characterize the intraportal vein islet transplantation (PV-Tx) mouse model.
• To propose PV-Tx as a suitable model for studying islet transplantation.
• To compare PV-Tx with kidney capsule transplantation (KC-Tx) in mice.

Main Methods:

• Syngeneic and allogeneic islet transplantation in C57BL/6 and BALB/C mice.
• Transplantation via portal vein (PV-Tx) and under the kidney capsule (KC-Tx).
• Monitoring of glucose levels and graft survival; histological evaluation of liver and kidney grafts.

Main Results:

• PV-Tx showed a significantly lower probability of achieving islet function compared to KC-Tx in both syngeneic and allogeneic models.
• Early glucose concentration post-infusion correlated with long-term graft function.
• Liver histology revealed adverse events (embolism, necrosis) in PV-Tx, absent in KC-Tx.
• Graft survival and outcomes differed between C57BL/6 and BALB/C mice, indicating strain-specific inflammatory responses.

Conclusions:

• The PV-Tx mouse model, despite lower initial success, mimics human islet transplantation more closely.
• PV-Tx is a valuable model for studying islet engraftment, immune suppression, and tolerance.
• Early post-transplant glycemic control is critical for long-term islet graft function.