XXXX mesenchymal stromal cells response to ionizing radiation.

@entity0 @entity19 @entity13698 @entity1958 @entity31796 @entity2006
BACKGROUND AIMS: This study evaluates the biological response of @entity1958 tissue-derived mesenchymal stromal cells (aMSCs) to ionizing radiation (IR). METHODS: Irradiated BALB/c @entity19 aMSCs were characterized for functionality and phenotype. The clonogenic capacity of irradiated aMSCs was assessed and compared with those of metastatic @entity0 cell line (4T1) and normal @entity19 fibroblasts (NIH3T3-wt). We investigated the IR-induced DNA damage response, apoptosis, changes in cell cycle (CC) dynamics and protein and gene expression. RESULTS: Irradiated and non-irradiated aMSCs were able to differentiate into adipocytes, chondrocytes and osteocytes with no significant difference. Irradiated aMSCs maintained the expression of mesenchymal stromal cells (MSCs) surface antigens and, as expected, were negative for hematopoietic stem cells (HSCs) surface antigens when tested up to 7 days after IR for all irradiation doses with no significant difference. Clonogenically, irradiated aMSCs had higher relative survival fraction and plating efficiency than 4T1 and NIH3T3-wt. Irradiated aMSCs expressed higher    @entity2006 and significantly showed faster and more time-efficient IR-induced DNA damage response evident by up-regulated @entity31796 and @entity13698 . Two hours after IR, most of aMSCs DNA damage/repair-related genes showed up-regulation that disappeared within 6   h after IR. Irradiated aMSCs showed a significant rise and an earlier peak of p-ATM-dependent and -independent (p84/5E10-mediated) G2/M CC arrest compared with 4T1 and NIH3T3-wt. CONCLUSIONS: After IR exposure, aMSCs showed a robust and time-efficient radiation-induced DNA damage repair response, stable phenotypical characteristics and multi-lineage differentiation potential, suggesting they may be reliable candidates for cell therapy in radiation oncology regenerative medicine.
