Impact of mesenchymal stromal cells and/or everolimus on T-reg lymphocyte expansion in rats

Background:
Mesenchymal stromal cells (MSC) are a promising cell-therapy in solid-organ transplantation, namely because of their immunomodulatory properties and positive impact on the expansion of T-regulator lymphocytes (Treg). The “optimal” immunosuppressive regimen to be associated with MSC has not been defined. Here, we aimed to evaluate the effects on Treg expansion of a single injection of MSC combined or not with everolimus in rats.
Materials and methods:
Twenty-four Lewis rats were randomly assigned to 4 groups (n=6 per group): MSC+Evero group, i.e. everolimus (0,25mg/kg/day, SC) from D0 to D14 and iv MSC (±1x106 cells) at D9; MSC group, i.e. placebo from D0 to D14 and iv MSC at D9; Evero group, i.e. everolimus from D0 to D14 and iv saline at D9; control group, i.e. placebo from D0 to D14 and iv saline at D9. T-reg blood levels were measured at D0-14-28 with flow cytometry analysis using anti-CD4,-CD25 and -FoxP3 antibodies.
Results:
In the two groups infused with MSC, Treg were significantly expanded at D14 and D28 (p<0.01), in comparison to D0. When compared to controls group, the “Evero” group showed a significant expansion of Treg levels at D14 but not at D28. In control, Treg levels did not significantly change compared to D0.
Conclusion: A single iv MSC injection was efficient to expand T-reg blood levels. This effect was not altered by everolimus co-administration. Everolimus exposure alone promotes a transient T-reg expansion. Hence, everolimus may be regarded as a co-drug of choice in MSC-based therapy in solid-organ transplantion.