Mesenchymal Stromal Cells Accelerate Hematopoietic Reconstitution and Mediate An IL6-Dependent Regeneration of the Intestinal Epithelium of Lethally Irradiated Mice.

Abstract 3846

Apoptosis of radiation-sensitive stem cells in the bone marrow and the gut are the main complications arising from radiation exposure, whether therapeutic or accidental. Bone marrow-derived mesenchymal stromal cells (MSC) were shown to exert regenerative properties through the secretion of factors which act in a paracrine manner. In this study, we demonstrated that a single intra-peritoneal injection of C57Bl/6 MSC rescued lethally irradiated Balb/c mice. Histological analysis and Ki67 immunostaining of jejunum sections collected 48 hours and 5 days post MSC injection indicated that MSC protected the gastro-intestinal epithelium from severe radiation-induced damages and prompted the regeneration of the gut by stimulating proliferation of the crypt stem cell pool. Using interleukin-6 null MSC, we demonstrated that IL-6 derived from the MSC played a role accelerating gastro-intestinal epithelium regeneration. We also observed that MSC injection prevented severe anemia and restored granulocyte and platelet counts to normal values faster than the control group. Accelerated regeneration of the bone marrow and extra-medullar hematopoiesis in the spleen of MSC transplanted mice corroborated this observation. Our results suggest that IL-6 derived from MSC or used on its own may be exploited to alleviate radiation induced injuries to patients undergoing radiotherapy or subject to accidental radiation exposure