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

Abstract

Dr Lan Yang and Dr Ying-Min Liang contributed equally to this workObjective: 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, FACSCalibur™ (BD Immunocytometry Systems, San Jose, CA), 5-ethynyl-29-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 500 cGy g-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.

The cytokine platelet factor 4 successfully replaces bovine serum albumin for the in vitro culture of porcine embryos

“…How PF4 exerts it effects on the embryos is yet unknown, but it has been reported that PF4 treatment of mesenchymal cells enhanced proliferation and apoptosis inhibition by the induction of differential expression of genes related to DNA reparation and cell cycle modulation [12]. In addition, PF4 supplementation during culture is involved in an increase in hematopoietic progenitor cell survival and differentiation.…”

“…To build on this point, it has been demonstrated that platelet factor 4 (PF4), which is a peptide member of the C-X-C chemokine family (also known as CXCL4), enhances hematopoietic stem cell survival [10] and hematopoietic stem cell differentiation into B cell lineage cells through STAT5 activation [11]. PF4 has also shown effects on bone marrow mesenchymal stem cells, protecting these cells from radiation injury and modulating the expression of genes related to the cell cycle and inhibition of apoptosis [12]. These actions in poorly differentiated cells led us to suspect that PF4 exhibits positive effects over embryonic cells.…”

Xenografting of human umbilical mesenchymal stem cells from Wharton’s jelly ameliorates mouse spinocerebellar ataxia type 1

“…FGF-2 is upregulated in the damage cerebellum to initiate neovascularization and facilitate neurogenesis [37] . Likewise, CXCL-14 may stimulate the proliferation, chemotaxis, and tube formation of endothelial cells and are essential for the development of blood vessels [38] . We speculate that some other cytokines and growth factors beyond the 174 that we assessed may also protect SCA1 cerebella.…”

Monitoring of platelet function parameters and microRNA expression levels in patients with prostate cancer treated with volumetric modulated arc radiotherapy

“…Although contradictory results exist in clinical studies investigating PF 4 levels in various types of cancer (53)(54)(55), to the best of our knowledge no clinical studies have focused on the changes in plasma PF 4 levels associated with RT. A number of in vitro studies have provided evidence of the protective effect of PF 4 against the damaging effect of radiation (56,57).…”