干细胞移植改善股骨头坏死缺血状态的实验及临床效应：20只模型兔及188例患者资料分析

背景：缺血性股骨头坏死由于股骨头局部滋养血管损伤、供血不足致病，迄今尚无最佳治疗方案，改善股骨头血液供应成为治疗本病的关键。目的：通过动物实验和临床观察，验证自体骨髓问充质干细胞移植血管再生技术改善股骨头坏死缺血状态的效果。设计：对比动物实验和自身对照临床观察。单位：解放军第四六三医院细胞治疗中心。资料：①动物：选用日本大耳白兔20只，雌雄不拘，体质量3．0—4．0kg，购于沈阳军区总医院动物实验中心。此动物实验符合动物伦理学要求。②对象：选择2004—07／2007—07在解放军第四六三医院细胞治疗中心住院的具有完整随访资料的缺血性股骨头坏死患者188例（335髋），男113例，女75例，年龄18-72岁。均经髋关节X线摄片、核素扫描、MRI、CT检查确诊；对治疗和实验知情同意。实验经医院伦理委员会批准。方法：①动物实验：实验于2004—01／2004—06在沈阳军区总医院动物实验中心完成。采用液氮冷冻股骨头缺血性坏死模型建立方法，双后肢股骨头均制作缺血模型，右侧为移植组，左侧为对照组。抽取骨髓，将所获单个核细胞经右股动脉注入；同法将生理盐水注入左侧股动脉内。②临床观察：密度梯度离心缺血性股骨头坏死患者自体骨髓，分离单个核细胞。行旋股内、旋股外及闭孔动脉干细胞移植术。主要观察指标：①4周后行DSA动脉造影观察双侧血管新生情况。4，12周后取双侧股骨头标本，行病理切片观察新骨再生及股骨头修复程度。②于移植后第3，6，12，24个月观察患者髋关节疼痛、行走间距及步态、髋关节外展与内旋功能变化。于干细胞移植后6个月行股骨头供血动脉造影术，观察血管新生及股骨头供血动脉充盈情况。于干细胞移植后6，12，24个月行CT，X射线，MRI检查，观察股骨?

Stem cell transplantation for ischemic femoral head necrosis--Analysis in 20 model rabbits and 188 patients

BACKGROUND： Iscbemic femoral head necrosis is caused by local vascular injury and blood-supply insufficiency. There exists no optimal treatment for the ischemic femoral head necrosis. Thus, the improvement of the blood supply to the femoral head seems to be a key point for the treatment.
OBJECTIVE： To verify the curative effects of autologous bone marrow mesenchymal stem cell transplantation induced vascular regeneration on the improvement of ischemic femoral head necrosis via animal experiments and clinical observations.
DESIGN： Contrast animal experiment and self-controlled clinical observation.
SETTING： Cell Therapy Center, the 463 Hospital of Chinese PLA.
MATERIALS AND PARTICIPANTS： ① Animals： Twenty Japanese white rabbits in either gender and weighing 3.0-4.0 kg were purchased from Animal EXperimental Center, General Hospital of Shenyang Military Area Command of Chinese PLA. The animal experiments were coincident with the ethical standards. ② Participants： 188 patients with ischemic femoral head necrosis （335 hips） having whole following-up data were selected from Cell Therapy Center, the 463 Hospital of Chinese PLA from July 2004 to July 2007. There were 113 males and 75 females, and their ages ranged from 18 to 72 years. Diagnosis was done by using X-ray photographs, nuclide scanning, MRI and CT examinations. All patients provided the informed consent, and the study was approved by the local research ethics committee.
METHODS： ① Animal experiments： The experiment was carried out at the Animal Experiment Center, General Hospital of Shenyang Military Area Command of Chinese PLA from January to June 2004. Ischemic femoral head necrosis models were established at both hindlimbs by using liquid-nitrogen refrigeration. The right side was regarded as transplantation group and the left one as control group. Mononuclear cells extracted from bone marrow were poured in the right femoral artery, while saline was poured in the left femoral artery. ②Clinical observations： Mononu