CCR2 expression is not necessary for the beneficial effects of mesenchymal/stromal cell-based therapy in DSS-induced colitis

M Lopez-Santalla(1) M A Martin(1) J A Bueren(1) M I Garin(1)

1:Division of Hematopoietic Innovative Therapies, Biomedical Innovation Unit, Centro de Investigaciones Energéticas Medioambientales y Tecnológicas (CIEMAT), Centre for Biomedical Network Research on Rare Diseases (CIBER-ER) and Advanced Therapy Unit, Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain.

Mesenchymal stem cells (MSCs) are currently used in preclinical and clinical studies for treatment of immune-mediated disorders thanks to their immunomodulatory and regenerative tissue properties. Numerous immune responses and mechanisms of action have been described for the immunomodulatory effects of MSCs although nowadays the precise mechanism of action remains to be fully defined. Previous data from the laboratory have demonstrated that in collagen-induced arthritis a transient increase of Ly6C-expressing monocytes was induced in peripheral blood upon infusion of MSCs that ultimately led to an increase of regulatory IL10-expressing macrophages in the draining lymph nodes. Hence, in this study, we aim to investigate whether the CCR2-mediated trafficking of immune cells is involved in the beneficial effects of MSC-based therapy. To address this, a clinically relevant mouse model of dextran sulphate sodium (DSS)-induced colitis using CCR2-deficient mice was used to study the trafficking of CCR2-expressing cell populations in vivo. Strikingly a single dose of allogeneic adipose-derived MSCs infused in DSS-induced colitic CCR2-deficient mice was as effective as in WT mice. These results suggest that in contrast to previously reported studies and to our initial hypothesis, the CCR2-mediated trafficking of immune cells is not involved in the mechanism of action mediated by infused MSCs in DSS-induced colitis.