The Relative Merits of Cord Blood as a Cell Source for Autologous T Regulatory Cell Therapy in Type 1 Diabetes.

Cord blood has been used as a cell source for therapeutic purposes in children with type 1 diabetes and other disorders. Here, we explore the benefits of cord blood as an autologous source of T regulatory cells for immune cell therapy in patients. CD4⁺ CD25⁺ T regulatory cells were isolated from cord blood and adult peripheral blood of healthy donors and compared during and after expansion in a 14-day protocol incorporating anti-CD3/anti-CD28 beads, and IL-2 with or without rapamycin. Cord blood T regulatory cells were largely naïve (89 ± 7 vs. 31 ± 10 % in young adults, p < 0.0001), and had higher expansion yields (median 5 968-fold) than adult T regulatory cells (median 516-fold, p = 0.001) and adult naïve T regulatory cells (median 820-fold, p = 0.003). Rapamycin reduced expansion yields, but was not necessary to obtain pure expanded cord blood T regulatory cells as judged by FOXP3 staining (94 ± 3 %), methylation status of FOXP3 (97 %), and intracellular effector cytokine staining (< 6 %). Expanded adult T regulatory cells were much less pure in the absence of rapamycin (72 ± 19 % FOXP3; 76 % by methylation status, < 13 % INF-γ, < 16 % IL-4, < 5 % IL-17 positive), but purity was achieved by inclusion of rapamycin during expansion. Despite differences in purity, all preparations of expanded T regulatory from all sources were able to strongly suppress proliferation of T effector cells in vitro. Our findings suggest that cord blood is an excellent source of T regulatory cells for expansion and autologous cell therapy that may be considered as a strategy to prevent immune-mediated destruction of beta cells in type 1 diabetes. [ABSTRACT FROM AUTHOR]