目的 股骨头坏死致高致残率和高髋关节置换手术率,目前缺乏有效逆转病情的治疗方法。通过观察超声引导下关节腔局部植入脐间充质干细胞治疗股骨头坏死的临床效果和安全性,探索股骨头坏死有效的治疗方法。方法 选择2017年1月—2019年9月在徐州医科大学附属医院收治的股骨头坏死接受人脐间充质干细胞治疗的患者21例,男14例,女7例,共29个髋关节（髋）。根据世界骨微循环研究协会（ARCO）的分期系统：Ⅱ期17髋,Ⅲ期12髋。在超声引导下髋关节腔内植入脐间充质干细胞1×107。VAS评分评估移植前、移植后3、6、12个月的疼痛变化,Harris评分法评估移植前、移植后3、6、12个月的髋关节功能,测算移植前、移植后12月MRI T1像上最大层面坏死面积评估影像学变化。采用SPSS 26.0对数据进行统计分析。结果 患者移植后疼痛改善：移植后3个月（5.29±1.59）分、6个月（3.76±1.22）分、12个月（2.10±0.70）分,VAS评分较移植前（6.86±1.31）分好转（P<0.05）。患者临床症状改善：患侧髋关节疼痛改善共19例（90.4%）;步态改善或行走距离延长共17例（80.9%）;关节活动范围改善共14例（66.6%）。Harris评分：移植前（62.76±10.08）分,移植后3个月（74.62±9.70）分、6个月（76.90±8.21）分和12个月（77.48±7.54）分,均较术前明显提高（P<0.05）。股骨头坏死面积：移植后12个月平均（187.27±11.01） mm2,较移植前（236.31±23.43） mm2明显缩小（P<0.05）。不良事件：3例患者出现移植后短期患侧关节疼痛加重,非甾体类止痛药治疗后缓解。未发生发热、胃肠道反应、局部感染等不良反应。结论 关节腔局部植入间充质干细胞可改善早、中期股骨头坏死患者的临床症状、关节功能,并可延缓或逆转影像学进展,有望成为股骨头坏死的新的治疗手段。
Objectives Osteonecrosis of the femoral head is a disease without effective treatment, and features a high disability rate and a high hip joint replacement rate. This study aims to observe the clinical effect and safety of local implantation of mesenchymal stem cells guided by ultrasound on femoral head necrosis, and explore an effective treatment method for the disease. Methods A total of 29 hip joints of 21 patients （14 males and 7 females） with osteonecrosis of the femoral head and undergoing treatment using umbilical mesenchymal stem cells were selected from January 2017 through September 2019 in the Affiliated Hospital of Xuzhou Medical University. According to the Association Research Circulation Osseous （ARCO） system, 17 hips were classified as stage II, and 12 hips as stage III. Umbilical mesenchymal stem cells （1×107） were implanted intra-articularly under ultrasonic localization. VAS score was used to evaluate pain changes before and at 3, 6, and 12 months after transplantation, Harris score was used to evaluate hip function at 3, 6, and 12 months after transplantation, and imaging results were measured in low-signal area at the maximum level of necrotic area on MRI T1 images before and at 12 months after transplantation. Statistical analysis was performed by SPSS 26.0. Results Postoperative pain was improved： VAS scores at postoperative 3 months （5.29±1.59）, 6 months （3.76±1.22）, and 12 months （2.10±0.70） were lower than that before transplantation （6.86±1.31, P<0.05）. Clinical symptoms were alleviated： 19 cases （90.4%） showed reduced pain of the affected side; 17 cases （80.9%） had improved gait or extended walking distance; 14 cases （66.6%） showed greater range of motion. Harris scores at postoperative 3 months （74.62±9.70）, 6 months （76.90±8.21）, and 12 months （77.48±7.54） were higher than that before transplantation （62.76±10.08, P<0.05）. The necrotic area was （187.27±11.01） mm2 at postoperative 12 months, which was significantly reduced compared with （236.31±23.43） mm2 before transplantation （P<0.05）. There were 3 patients with aggravation of short-term joint pain on the affected side after transplantation, which was alleviated after non-steroidal anti-inflammatory drug treatment. No adverse reactions such as fever, gastrointestinal reactions, or local infections occurred. Conclusion Local implantation of mesenchymal stem cells can alleviate clinical symptoms, improve joint function, and delay or reverse the imaging progress of patients with early and middle-stage osteonecrosis of the femoral head, which is expected to be a new treatment for femoral head necrosis.
[1] Moya-Angeler J, Gianakos AL, Villa JC, et al.Current concepts on osteonecrosis of the femoral head[J]. World J Orthop, 2015, 6(8):590-601.
[2] Baig SA, Baig MN.Osteonecrosis of the femoral head: etiology, investigations, and management[J]. Cureus, 2018,10(8):3171.
[3] Petek D, Hannouche D, Suva D.Osteonecrosis of the femoral head: pathophysiology and current concepts of treatment[J]. Efort Open Rev, 2019, 4(3):85-97.
[4] Li R, Lin QX, Liang XZ, et al.Stem cell therapy for treating osteonecrosis of the femoral head: From clinical applications to related basic research[J]. Stem Cell Res Ther, 2018, 9(1):291.
[5] 王楠,刘伟,周晔.髓芯减压植骨术联合脐带间充质干细胞移植治疗股骨头坏死的疗效[J].中国老年学杂志, 2013, 33(23):5862-5864.
[6] Kang JS, Suh YJ, Moon KH, et al.Clinical efficiency of bone marrow mesenchymal stem cell implantation for osteonecrosis of the femoral head: a matched pair control study with simple core decompression[J]. Stem Cell Res Ther, 2018, 9(1):274.
[7] Zhao D, Cui D, Wang B, et al.Treatment of early stage osteonecrosis of the femoral head with autologous implantation of bone marrow-derived and cultured mesenchymal stem cells[J]. Bone, 2012, 50(1):325-330.
[8] 张鹤山,李子荣.股骨头坏死诊断与治疗的专家建议[J].中华骨科杂志, 2007, 27(2):146-148.
[9] Sun W, Wang B L, Li Z R.Chinese specialist consensus on diagnosis and treatment of osteonecrosis of the femoral head[J]. Orthop Surg, 2011, 3(2):131-137.
[10] Dominici M, Le Blanc K, Mueller I, et al.Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement[J].Cytotherapy,2006, 8(4):315-317.
[11] Harris WH.Traumatic arthritis of the hip after dislocation and acetabular fractures: treatment by mold arthroplasty. An end-result study using a new method of result evaluation[J].J Bone Joint Surg Am, 1969, 51(4):737-55.
[12] 刘江锋. 髓芯减压联合自体骨髓间充质干细胞移植治疗股骨头坏死[J].中国组织工程研究,2019, 23(29):4599-4604.
[13] Zhao DW, Yu M, Hu K, et al.Prevalence of nontraumatic osteonecrosis of the femoral head and its associated risk factors in the Chinese population: results from a nationally representative survey[J]. Chin Med J (Engl), 2015,128(21):2843-2850.
[14] Zhao D, Liu Y, Ma C, et al.A mini review: stem cell therapy for osteonecrosis of the femoral head and pharmacological aspects[J]. Curr Pharm Des, 2019, 25(10): 1099-1104.
[15] Lieberman JR, Berry DJ, Mont MA, et al.Osteonecrosis of the hip: management in the 21st century[J]. Instr Course Lect, 2003, 52(1):337-355.
[16] Hernigou P, Lambotte JC.Volumetric analysis of osteonecrosis of the femur-anatomical correlation using MRI[J]. J Bone Joint Surg Br, 2001,83(5):672-675.
[17] Ma Y, Wang T, Liao J, et al.Efficacy of autologous bone marrow buffy coat grafting combined with core decompression in patients with avascular necrosis of femoral head: a prospective, double-blinded, randomized, controlled study[J]. Stem Cell Res Ther, 2014, 5(5):115.
[18] Tateishi-Yuyama E, Matsubara H, Murohara T, et al.Thera-peutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial[J].The Lancet, 2002,360(9331):427-435.
[19] 韩忠朝,王伟强.间充质干细胞的生物学特性及临床应用[J].中国科学(生命科学), 2017, 47(12):1404-1409.
[20] Lee JS, Roh HL.Alterations in the differentiation ability of mesenchymal stem cells in patients with nontraumatic osteonecrosis of the femoral head: comparative analysis according to the risk factor[J]. J Orthop Res, 2006, 24(4):604-609.
[21] Houdek MT, Wyles CC, Packard BD, et al.Decreased osteogenic activity of mesenchymal stem cells in patients with corticosteroid-induced osteonecrosis of the femoral head[J].J Arthroplasty, 2016, 31(4):893-898.
[22] 曲志国,野向阳,林辉.人脐带间充质干细胞诱导成骨及治疗骨缺损[J].中国组织工程研究与临床康复, 2011, 15(45): 8503-8507.
