Non-cultured adipose-derived cells promote the bone augmentation induced by low-dose BMP2

摘要

BMP2 has been shown to induce bone formation in a variety of indications on bone engineering, and is now recognized as one of most effective materials that can confer osteolnducibility to bone substitutes. However, direct implantation of high doses of BMP2 is known to induce substantial swelling that may cause the obstruction of airway when applied to oral and cervical areas. On the other hand, recent studies have shown adipose-tissue contains on the order of 100- to 500-fold more MSCs than do bone-marrow after initial harvest Therefore, non-cultured adipose-derived cells (NC-ADCs) including high densities of stem/progenitor cells may possess a stronger bone regenerative capability and effectively reduce the amounts of 8MP2 required to induce bone formation. Our aim is to investigate whether NC-ADCs can promote the bone augmentation induced by low-dose BMP2. For experiments, human ADCs were isolated by enzymatically dissociation after surgical removal of buccal fat-pad. Then, NC-ADCs were obtained after centrifugation to separate the mature adipocytes. After characteristics analyses in vitro, 3×106 NC-ADCs were mixed with β-TCP granules that absorbed low-dose BMP2. and were transplanted to onlay-placement on mice cranium. Other four groups were transplanted as experimental controls. After 2 and 4 weeks, the specimens were harvested and observed histologically. As findings, remarkable augmented bone-area were observed at 2 weeks of transplantation when NC-ADCs were transplanted with low-dose BMP2. Furthermore, ectopic bone formation could be clearly recognized in those specimens at 4 weeks. This suggests NC-ADCs can facilitate the clinical use of BMP2 for bone engineering.