Craniofacial Research Laboratory, Section of Plastic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Stem Cells Dev. 2013 Jun 1;22(11):1625-32. doi: 10.1089/scd.2012.0472. Epub 2013 Feb 19.
This study utilized transplanted bone marrow stromal cells (BMSCs) as a cellular replacement therapy to remedy radiation-induced injury and restore impaired new bone formation during distraction osteogenesis (DO). BMSC therapy brought about the successful generation of new bone and significantly improved both the rate and quality of a bony union of irradiated, distracted [X-ray radiation therapy (XRT)/DO] murine mandibles to the level of nonirradiated DO animals. The bone mineral density and bone volume fraction were also significantly improved by the BMSC replacement therapy showing no difference when compared to nonirradiated animals. Finally, a biomechanical analysis examining the yield, failure load, and ultimate load also demonstrated a significantly improved structural integrity in BMSC-treated XRT/DO mandibles over XRT/DO alone. These results indicate that administration of BMSCs intraoperatively to a radiated distraction gap can function as an adequate stimulant to rescue the ability for irradiated bone to undergo DO and produce a healed regenerate of a vastly superior quality and strength. We believe that the fundamental information on the optimization of bone regeneration in the irradiated mandible provided by this work has immense potential to be translated from the bench to the bedside to lead to improved therapeutic options for patients suffering from the disastrous sequelae of radiation therapy.
本研究利用骨髓基质细胞(BMSCs)作为细胞替代疗法,以弥补辐射诱导损伤,并在牵张成骨(DO)过程中恢复受损的新骨形成。BMSC 治疗成功地产生了新骨,并显著提高了照射、牵张(X 射线放射治疗(XRT)/DO)鼠下颌骨的骨融合率和质量,使其达到未照射 DO 动物的水平。BMSC 替代治疗还显著提高了骨矿物质密度和骨体积分数,与未照射动物相比无差异。最后,生物力学分析检查屈服、失效负荷和极限负荷也表明,BMSC 治疗的 XRT/DO 下颌骨在结构完整性方面明显优于 XRT/DO 单独治疗。这些结果表明,在辐射性牵张间隙中术中给予 BMSCs 可以作为一种充分的刺激物,挽救受照射骨进行 DO 的能力,并产生质量和强度大大提高的愈合再生体。我们相信,本研究提供的关于优化辐射下颌骨骨再生的基本信息具有从实验室转化为临床的巨大潜力,从而为遭受放射治疗灾难性后果的患者提供更好的治疗选择。