Janus Jeffrey R, Jackson Ryan S, Lees Katherine A, Voss Stephen G, Wilson Zachary C, Remmes Nicholas B, Keeney Michael G, Garcia Joaquin J, San Marina Serban
1 Department of Otorhinolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, Minnesota, USA.
2 Department of Otolaryngology-Head and Neck Surgery, Washington University, St Louis, Missouri, USA.
Otolaryngol Head Neck Surg. 2017 Apr;156(4):616-621. doi: 10.1177/0194599816688647. Epub 2017 Jan 24.
Objective Human adipose-derived mesenchymal stem cells (ADSCs) were used to rehabilitate bone damaged by osteoradionecrosis (ORN) in an established animal model. Study Design Prospective animal study. Setting Academic department laboratory. Subjects and Methods After institutional review board and Institutional Animal Care and Use Committee approval, 24 athymic nude rats were divided into 5 groups: 4 groups irradiated (20 Gy) by brachytherapy catheter placed at the left hemimandible and 1 mock irradiation control (n = 4). For all groups, ORN was initiated by extraction of the central molar 1 week later. After 28 days, animals (n = 5/group) received injection at the extraction site with saline (SAL), ADSCs, platelet-rich plasma and collagen (PRP/COL), or ADSCs + PRP/COL. Rats were sacrificed 28 days later and their mandibles harvested for histopathology analysis (osteoblasts, osteoclasts, and fibrosis) and bone volume measurement using 3-dimensional micro-computed tomography. Results All but 1 rat survived the experiment period (23/24). Radiographic and histological analysis revealed 60% bone loss in the SAL group compared with the nonirradiated control. Injection of ADSCs increased jaw region bone volume by up to 36% ( P < .01). All experimental groups (ADSC, PRP/COL, and ADSC + PRP/COL) showed dramatically decreased osteoclast counts ( P < .001) while injection of PRP/COL with or without ADSCs increased osteoblasts. Increased fibrosis was observed after ADSC injection ( P < .05). Conclusion The application of human ADSCs to an induced mandibular osteoradionecrosis model in athymic rats results in increased deposition or preservation of bone, demonstrated both histologically and radiographically. This offers an encouraging possible treatment option for translational research in this difficult disease.
目的 在已建立的动物模型中，使用人脂肪间充质干细胞（ADSCs）修复放射性骨坏死（ORN）损伤的骨组织。研究设计 前瞻性动物研究。研究地点 学术部门实验室。对象与方法 经机构审查委员会和机构动物护理与使用委员会批准后，将24只无胸腺裸鼠分为5组：4组通过置于左半下颌骨的近距离治疗导管接受照射（20 Gy），1组为假照射对照组（n = 4）。所有组在1周后拔除中央磨牙以引发ORN。28天后，动物（每组n = 5）在拔牙部位注射生理盐水（SAL）、ADSCs、富血小板血浆和胶原蛋白（PRP/COL）或ADSCs + PRP/COL。28天后处死大鼠，采集下颌骨进行组织病理学分析（成骨细胞、破骨细胞和纤维化），并使用三维微计算机断层扫描测量骨体积。结果 除1只大鼠外，所有大鼠均存活至实验期结束（23/24）。影像学和组织学分析显示，与未照射对照组相比，SAL组骨丢失60%。注射ADSCs使颌骨区域骨体积增加高达36%（P <.01）。所有实验组（ADSC、PRP/COL和ADSC + PRP/COL）破骨细胞计数均显著减少（P <.001），而注射PRP/COL（无论有无ADSCs）均增加了成骨细胞数量。注射ADSCs后观察到纤维化增加（P <. 05）。结论 将人ADSCs应用于无胸腺大鼠诱导的下颌骨放射性骨坏死模型，在组织学和影像学上均显示骨沉积或保留增加。这为这种难治性疾病的转化研究提供了一个令人鼓舞的可能治疗选择。
