Distraction osteogenesis (DO) is a widely used bone regenerative technique. However, the DO process is slow, and the consolidation phase is long. Therefore, it is of great clinical significance to explore the mechanism of DO, and shorten its duration. Recent studies reported that stem cell exosomes may play an important role in promoting angiogenesis related to DO, but the mechanism remains unclear.Distraction osteogenesis (DO) is a widely used bone regenerative technique. Its osteogenesis rate is 4–6 times that of a normal child development. However, the DO process is slow, and the consolidation phase is long. Thus, it is inconvenient to patient life, and enhances complication risks. Therefore, it is of great clinical value to explore the mechanism of DO, and shorten its duration. Blood vessels determine the local microenvironment in the skeletal system, and they play a crucial role in osteogenesis. Successful bone formation is highly dependent on neovascularization, and it involves a multi-layered and mutually responsive biological regulatory network that interlinks neovascularization and bone regeneration , which, is known as osteogenic-angiogenic coupling effect. Unfortunately, inadequate blood supply during the consolidation phase can lead to multiple complications, including, nonunion and delayed union. Therefore, it is of great significance to examine the DO-based angiogenesis mechanism to accelerate bone formation, and shorten DO duration.

Endothelial progenitor cells (EPCs) differentiate to form endothelial cells that are critical for angiogenesis. Circulating EPCs tend to increase during DO distraction and consolidation phases, and cultured and labeled EPCs are recruited to the distraction areas. Endothelial colony-forming cells (ECFCs) or late EPCs, have strong proliferation ability, and form new blood vessels in vivo. They are often considered as "endothelial progenitor cells" because of their ability to produce endothelial cell progeny in a true sense. ECFCs generally stimulate vascular repair through multiple mechanisms, such as, physical engraftment within neovascularization, paracrine release of pro-angiogenic mediators, secretion of exosomes, and synergy with other cells, and the activation of multiple mechanisms that synergistically promotes tissue revascularization. Studies have shown that ECFCs secrete exosomes, which are key to their beneficial effects.

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Mishita
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Journal of Heart and Cardiovascular Research