This PhD thesis explores novel strategies to improve outcomes in islet cell transplantation for type 1 diabetes by addressing both immune-related and engraftment challenges. A combination therapy of low-dose anti-CD3 monoclonal antibodies and genetically modified Lactococcus lactis producing proinsulin and IL-10 was shown to prevent autoimmune diabetes recurrence in 56% of long-term diabetic NOD mice, with timing of treatment and disease duration being key factors. The study also demonstrated that human multipotent adult progenitor cells (MAPC®), when co-transplanted with islets, enhance graft revascularization and function by secreting angiogenic factors and promoting capillary formation. Together, these findings suggest that integrating antigen-specific tolerance induction with cellular strategies to support engraftment can significantly improve islet graft survival and function. Ultimately, this work presents promising therapeutic avenues for achieving long-term success in beta-cell replacement therapies for type 1 diabetes.
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