Engineered immunomodulatory accessory cells improve experimental allogeneic islet transplantation without...

Area of Science:

• Immunology
• Regenerative Medicine
• Diabetes Research

Background:

• Islet transplantation is a treatment for type 1 diabetes.
• Systemic immunosuppression poses significant side effects, often outweighing transplantation benefits.
• Novel strategies are needed to mitigate immunosuppression in islet transplantation.

Purpose of the Study:

• To engineer mesenchymal stromal cells (MSCs) to support islet transplantation.
• To evaluate the efficacy of engineered MSCs (eMSCs) in improving islet allograft survival without systemic immunosuppression.
• To investigate the immunomodulatory mechanisms of eMSCs in islet transplantation.

Main Methods:

• Engineered MSCs (eMSCs) by modifying them with programmed death ligand-1 and CTLA4-Ig fusion protein.
• Cotransplanted eMSCs with islets in syngeneic and allogeneic diabetic mouse models.
• Assessed islet allograft survival and performed immunophenotyping of infiltrating immune cells.

Main Results:

• eMSCs significantly improved islet transplantation outcomes in both syngeneic and allogeneic models.
• Allografts survived up to 100 days without systemic immunosuppression when cotransplanted with eMSCs.
• Immunophenotyping showed reduced T effector cell infiltration and increased T regulatory cell infiltration in eMSC-treated grafts.

Conclusions:

• Engineered MSCs (eMSCs) effectively induce local immunomodulation, promoting islet allograft survival.
• This strategy may reduce or eliminate the need for systemic immunosuppression in clinical islet transplantation.
• eMSCs offer a promising approach to ameliorate the negative impacts of immunosuppression in type 1 diabetes treatment.