Egashira Kazuhiro, Sumita Yoshinori, Zhong Weijian, I Takashi, Ohba Seigo, Nagai Kazuhiro, Asahina Izumi
Department of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Basic and Translational Research Center for Hard Tissue Disease, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
PLoS One. 2018 Jan 18;13(1):e0191099. doi: 10.1371/journal.pone.0191099. eCollection 2018.
Bone marrow concentrate (BMC), which is enriched in mononuclear cells (MNCs) and platelets, has recently attracted the attention of clinicians as a new optional means for bone engineering. We previously reported that the osteoinductive effect of bone morphogenetic protein-2 (BMP-2) could be enhanced synergistically by co-transplantation of peripheral blood (PB)-derived platelet-rich plasma (PRP). This study aims to investigate whether BMC can effectively promote bone formation induced by low-dose BMP-2, thereby reducing the undesirable side-effects of BMP-2, compared to PRP. Human BMC was obtained from bone marrow aspirates using an automated blood separator. The BMC was then seeded onto β-TCP granules pre-adsorbed with a suboptimal-dose (minimum concentration to induce bone formation at 2 weeks in mice) of recombinant human (rh) BMP-2. These specimens were transplanted subcutaneously to the dorsal skin of immunodeficient-mice and the induction of ectopic bone formation was assessed 2 and 4 weeks post-transplantation. Transplantations of five other groups [PB, PRP, platelet-poor plasma (PPP), bone marrow aspirate (BM), and BM-PPP] were employed as experimental controls. Then, to clarify the effects on vertical bone augmentation, specimens from the six groups were transplanted for on-lay placement on the craniums of mice. The results indicated that BMC, which contained an approximately 2.5-fold increase in the number of MNCs compared to PRP, could accelerate ectopic bone formation until 2 weeks post-transplantation. On the cranium, the BMC group promoted bone augmentation with a suboptimal-dose of rhBMP-2 compared to other groups. Particularly in the BMC specimens harvested at 4 weeks, we observed newly formed bone surrounding the TCP granules at sites far from the calvarial bone. In conclusion, the addition of BMC could reduce the amount of rhBMP-2 by one-half via its synergistic effect on early-phase osteoinduction. We propose here that BMC transplantation facilitates the clinical use of rhBMP-2 as an alternative strategy for bone engineering.
骨髓浓缩物（BMC）富含单核细胞（MNCs）和血小板，最近作为骨工程的一种新的可选手段引起了临床医生的关注。我们之前报道过，通过共同移植外周血（PB）来源的富血小板血浆（PRP），骨形态发生蛋白-2（BMP-2）的骨诱导作用可得到协同增强。本研究旨在调查与PRP相比，BMC是否能有效促进低剂量BMP-2诱导的骨形成，从而减少BMP-2的不良副作用。使用自动血液分离器从骨髓抽吸物中获取人BMC。然后将BMC接种到预先吸附有次优剂量（小鼠中诱导2周骨形成的最低浓度）重组人（rh）BMP-2的β-TCP颗粒上。将这些标本皮下移植到免疫缺陷小鼠的背部皮肤，并在移植后2周和4周评估异位骨形成的诱导情况。其他五组移植[PB、PRP、贫血小板血浆（PPP）、骨髓抽吸物（BM）和BM-PPP]用作实验对照。然后，为了阐明对垂直骨增量的影响，将六组的标本移植到小鼠颅骨上进行覆盖放置。结果表明，与PRP相比，BMC中MNCs数量增加了约2.5倍，在移植后2周内可加速异位骨形成。在颅骨上，与其他组相比，BMC组用次优剂量的rhBMP-2促进了骨增量。特别是在4周时收获的BMC标本中，我们在远离颅骨的部位观察到TCP颗粒周围有新形成的骨。总之，通过其对早期骨诱导的协同作用，添加BMC可将rhBMP-2的用量减少一半。我们在此提出，BMC移植有助于rhBMP-2在临床上作为骨工程的替代策略使用。
