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

BACKGROUND: Ischemic 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: Mononuclear cells were separated from autologous bone marrow of patients with ischemic femoral head necrosis after density gradient centrifugation. MAIN OUTCOME MEASURES: ①Four weeks later, angiogenesis at both femoral arteries was observed by arteriography by using digital subtraction anglography (DSA). Moreover, bilateral femoral head samples underwent pathological sections to observe bone regeneration and repair of femoral head 4 and 12 weeks later. ②Items including hip pain, walking distance and gait, abduction and internal rotation function changes of hip joint were observed in 3, 6, 12 and 24 months after stem cell transplantation in media femoral circum flex artery, lateral femoral circum flex artery and obturator artery. In 6 months after stem cell transplantation, angiogenesis and blood supply of femoral head were observed by using arteriography. In 6, 12 and 24 months after stem cell transplantation, morphological and ischemic changes of femoral head were observed by using CT, X-ray and MRI examinations. Harris scores were used to evaluate function of hip joint before and in 3, 6, 12 and 24 months after stem cell transplantation.RESULTS: Animal experiment: Twenty rabbits were involved in the final analysis. ① DSA-arteriography results: In 4 weeks after transplantation, blood-supply arteries in femoral head of right hindlimb in the transplantation group were more than those in the control group. ② Pathological results: In 12 weeks after transplantation, cartilage, lamellar bone and bone trabecula in the left femoral head were repaired remarkably, but left femoral head necrosis was not improved. Clinical observations: 188 patients were involved in the final analysis. ① Improvement of symptoms: Among 188 patients, 164 (87.3%) had remission of hip pain, 147 (78.4%) had function improvement, and 150 (80.0%) had elongation of walking distance. ② Imaging changes: At 6 months after transplantation, DSA-arteriography in 12 patients demonstrated that blood-supply arteries in femoral head were increased and thickened remarkably as compared with those before transplantation, and the blood flow was rapid. At 12-24 months after transplantation, lesion of bone matrix in 24 patients was improved under the X-ray, CT and MRI examinations. ③ Harris scores of hip joint: The scores at 6, 12 and 24 months after transplantation were significantly higher than those before transplantation (t= -3.423, -6.714, -9.039, P < 0.01).CONCLUSION: Autologous bone marrow mesenchymal stem cell transplantation can effectively improve and treat ischemic femoral head necrosis.

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