Platelet factor 4 protects bone marrow mesenchymal stem cells from acute radiation injury

Objective: The aim of this study was to find a new radiation protector, platelet factor 4 (PF4) and to identify its effect on haemopoietic microenvironment in vitro and in vivo. Methods: Radiation damage on bone marrow mesenchymal stem cells ex and in vitro was set up as models. Growth curve analysis, clonogenic survival assay, FACS-Calibur (TM) (BD Immunocytometry Systems, San Jose, CA), 5-ethynyl-2'-deoxyuridine immunofluorescence staining and quantitative reverse transcription-polymerase chain reaction were employed to assess the characterization of bone marrow mesenchymal stem cells (BMSCs), proliferation, apoptosis, cell cycle and gene expression. Results: A dose-and time-dependent enhancement of cell viability and survival was observed for PF4 treatment along with 500cGy gamma-radiation in vitro. The same phenomena were noted in vivo, including enhancement of adherence and proliferation ability while inhibition of cell apoptosis, which were associated with a short-term decrease in the G0/G1 ratio owing to S phase arrest. These were accompanied with enhanced Bcl-2 expression and p53/p21 loss. Conclusion: These results uncover that PF4 might be a novel therapeutic approach, which could reduce DNA damage and increase survival of BMSCs, in part, by inhibiting p53/p21 axis and facilitating DNA damage repair. Advances in knowledge: This study explores the feasibility of a new radioprotector and hence may be clinically important.