No treatment to halt the progressive loss of insulin-producing beta-cells in type 1 diabetes mellitus has yet been clinically introduced. Strategies tested have at best only transiently preserved beta-cell function and in many cases with obvious side effects of drugs used. Several studies have suggested that mesenchymal stromal cells exert strong immunomodulatory properties with the capability to prevent or halt diabetes development in animal models of type 1 diabetes. A multitude of mechanisms has been forwarded to exert this effect. Recently, we translated this strategy into a first clinical phase I/IIa trial and observed no side effects, and preserved or even increased C-peptide responses to a mixed meal tolerance test during the first year after treatment. Future blinded, larger studies, with extended follow-up, are clearly of interest to investigate this treatment concept.