Regulatory cell-based therapies, encompassing stem-like cells, T regulatory cells, and tolerogenic dendritic cells, have already been tested in clinical trials for reversing autoimmunity in type 1 diabetes. These early successes opened new perspectives for next-generation antigen-specific strategies to achieve durable and self-sustaining immune tolerance.
ABSTRACT
Type 1 diabetes (T1D) is an autoimmune disorder characterized by the destruction of insulin-producing β-cells in the pancreas. Despite advances in insulin therapy and β-cell replacement, a definitive cure addressing the underlying cause of the disease, that is the loss of immune tolerance to β-cells remains elusive. Emerging strategies to reshape the immune response to pancreatic autoantigens include the adoptive transfer of ex vivo cultured regulatory cells, either mesenchymal stem cells (MSCs), regulatory T cells (Tregs), or dendritic cells (DCs), collectively known as regulatory cell therapy. This review aims to provide an overview of the regulatory cell-based approaches for T1D currently under development. Although several clinical trials have demonstrated the safety of in vivo administration of regulatory cells to T1D patients, only mild signs of efficacy have been reported. The most promising results were observed in patients with shorter disease duration and higher residual β-cell mass, suggesting that early interventions may result in clinical benefit. Significant challenges remain, including the long-term efficacy and stability of the infused products. In the future, approaches combining regulatory cell-based therapies with immunomodulatory agents or strategies to restore the damaged insulin-producing cells may hold the key to achieving a functional cure for T1D.