Advances in the Masquelet technique: Myeloid-derived suppressor cells promote angiogenesis in PMMA-induced membranes

摘要

The periosteum plays a critical role in bone formation and defect reconstruction. The concept of tissue engineering in the periosteum has been suggested to solve the clinical problems related to bone defect repair. Insertion of polymethyl methacrylate (PMMA) bone cement can induce the autologous generation of a tissue-engineered periosteum and has been considered as a promising strategy for bone defect reconstruction. The PMMA-induced membrane is a crucial element in the reconstruction of bone defects, especially for angiogenesis, but its biological mechanism remains elusive. Here, a PMMA-induced membrane model was established using a femoral critically sized defect in mice. We identified myeloid-derived suppressor cells (MDSCs) as a regulatory component of induced membrane vascularization. The increased number of MDSCs was markedly linked to increased membrane thickness and capillary density. Importantly, the results of an in vitro coculture assay indicated that MDSCs of the induced membrane further facilitated the angiogenic capacity of human umbilical vein endothelial cells (HUVECs) by upregulating the expression of VEGFA, Ang2 and HIF-1 alpha. Furthermore, signaling pathway blockade results suggested that STAT3 activation is involved in the upregulation of VEGFA, Ang2 and HIF-1 alpha expression in induced membrane MDSCs. Our findings provide new insights into the mechanism of angiogenesis in the PMMA-induced membrane and confirm the key signaling molecules of MDSCs in induced membrane angiogenesis. Based on these results, this strategy may become a new therapy for the treatment of large bone defects in the future.