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Despite advances in insulin therapy and \u03b2\u2010cell replacement, a definitive cure addressing the underlying cause of the disease, that is the loss of immune tolerance to \u03b2\u2010cells 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\u2010based 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 \u03b2\u2010cell mass, suggesting that early interventions may result in clinical benefit. Significant challenges remain, including the long\u2010term efficacy and stability of the infused products. In the future, approaches combining regulatory cell\u2010based therapies with immunomodulatory agents or strategies to restore the damaged insulin\u2010producing cells may hold the key to achieving a functional cure for T1D.<\/jats:p>","DOI":"10.1002\/eji.202451722","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:13:57Z","timestamp":1748391237000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Advances in Regulatory Cell Therapy for Type 1 Diabetes: Emerging Strategies and Future Directions"],"prefix":"10.1002","volume":"55","author":[{"given":"Laura","family":"Passerini","sequence":"first","affiliation":[{"name":"Mechanisms of Peripheral Tolerance Unit San Raffaele Telethon Institute for Gene Therapy (SR\u2010Tiget) IRCCS San Raffaele Scientific Institute  Milan 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