Differences In Angiogenesis Between Different Embryonic Human BMSCs

Developmental biology has confirmed that and limbs are derived from different sources of embryogenesis(cranial-maxillofacial bone orgins from mesenchymal of cranial neural crest trunk while limbs from mesoderm).Researches showed that these two different embryonic bones contained bone marrow mesenchymal stem cells(BMSCs)of remarkable unique function,and may be one of the key factors that affect bone graft healing.In recent years,much attention has been paid to the ability of BMSCs pro-angiogenesis.BMSCs transplantation effectively improves the survival of myocardial ischemia.Angiogenesis is the beginning of bone healing and crucial for bone defect repair processing.Therefore,from the perspective of angiogenesis,the functional differences between these two BMSCs in angiogenesis,not only reveal the ectopic bone graft healing mechanism but also can provide new clues and theoretical basis for jaw bone defect repair.Under ischemia and hypoxia environment,the endothelial cells are raised to bone defect area in the form of budding gathering themselves together,and finally mature to functional new blood vessels.In this process,the endothelial cells can produce bone morphogenetic proteins(BMPs)and vascular endothelial growth factor(VEGF),which are important to the early process of bone remodeling.The distraction osteogenesis(DO)experiments have confirmed that BMP-2 in bone distraction area is mainly produced by endothelial cells,while angiogenesis inhibition will affect bone formation and eventually lead to fibrous bone nonunion.More importantly,bone cells,including BMSCs,osteoblast and osteoclast,can secrete angiogenic growth factors and cytokines to promote angiogenesis through paracrine mechanism.Therefore,the close relationship between angiogenesis and osteogenesisa and the cell to cell communication between endothelial cells and bone cells determine the final outcomes of bone healing.This study using BMSCs and human umbilical vein endothelial cells(HUVECs)co-culture system,for the first time confirmed that the angiogenic vatiation between BMSCs from jaw bone and ilium in vivo and in vitro,with stronger angiogenic ability of jaw bone BMSCs compared with ilium BMSCs.We also found basic fibroblast growth factor(bFGF)expressed differently in the co-culture system.bFGF,a member of the fibroblast growth factor family,through combining with FGF receptors(FGFR)on the surface of the target cells,can activate signaling pathways related to proliferation and migration by raising a variety of protease,growth factor and integrins.The expression of bFGF in jaw bone BMSCs co-culture system was higher than ilium BMSCs co-culture system.Furthermore,the supernatant of jaw bone BMSCs could have stronger effects of proliferation and migration on HUVECs.The-exogenous bFGF.can enhance the angiogenic activity of ilium BMSCs while FGFR inhibitors(BGJ398)can inhibit the jaw bone BMSCs induced HUVECs sprouting.The results of present study showed that angiogenic variation between BMSCs from jaw bone and ilium and this may be associated with different levels of bFGF expression.