Abstract 13756: The Hematopoietic and Megakaryocytic Protective Effect of PDGF-BB on Radiation-Induced Myelosuppression Model

Introduction: Platelet-derived growth factors (PDGF) was initially purified from platelets and characterized as a mitogen for fibroblasts and smooth muscle cells. The PDGF family comprises four different genes that form at least five different dimers, including PDGF-AA, AB, BB, CC and DD. In the hematopoietic system, genetic studies have reported that knock-out mice for PDGF-BB show anemia and thrombocytopenia. PDGF also stimulates the proliferation of megakaryocytes, erythrocytes, leukocytes, and their progenitors, and enhances the expansion of megakaryocyte progenitors from human CD34+ cells. Methods: Blood counts, bone marrow histology, and CFU were performed to investigate the protective effect of PDGF-BB on mice bone marrow hematopoiesis. Flow cytometry was used to detect early apoptosis (Annexin V), mitochondrial membrane potential (JC-1) and Caspase-3 of Meg-01. Results: Peripheral blood count showed that PDGF stimulated the recovery of white blood cells and platelets on radiation-induced myelosuppression model (P<0.01, n=4). Bone marrow histology showed that the numbers of megakaryocytes and their progenitor cells were higher than that in PDGF-BB group. PDGF-BB significantly stimulated the formation of CFU-MK, CFU-GM, BFU-E and CFU-F (P<0.01, n=4). PDGF-BB had a dose-dependent effect on cell proliferation in the range of 5-50 μg/mL in vitro (P<0.001, n=4). Late apoptotic and necrotic cells (Annexin V +, PI +) and total dead cells (Annexin V +) were decreased in the PDGF-BB (50 μg/ml) group (P<0.01, n=4). The mitochondrial membrane potential in the PDGF-BB group was increased when compared with control group, which indicated that the number of apoptotic cells was decreased (P<0.01, n=4). Besides, the expression of Caspase-3 in PDGF-BB treatment group was also lower than that in control group (P<0.05, n=4). Conclusions: PDGF-BB has a hematopoietic protective effect on the myelopoietic mice model, especially on megakaryocytes and their progenitor cells. It has proliferative and anti-apoptotic effects on Meg-01, and the mechanism may be mediated through JC-1 and Caspase-3 pathway.