自体骨髓间充质干细胞联合周围神经移植治疗脊髓损伤**★
李志营1,步星耀1,张圣旭1,梁庆华1,李太平1,陈书连2,李六一3,赵耀武4,翟亚平5,张永福1
相关链接:美国Kao 等用自体周围神经移植治疗脊髓损伤,术后发现再生轴突通过移植的周围神经重新恢复了脊髓损伤的连续性,截痪的肢体功能有部分恢复。中国第二、三军医大学等探讨不同条件下周围神经移植修复脊髓损伤的能力,虽然能提高损伤脊髓的再生能力,但其作用微弱,无明显的功能性恢复。骨髓间充质干细胞可在中枢神经系统内成活并可分化成为神经样细胞,将其移植于脊髓损伤部位后,实验动物瘫痪肢体的肌力得到部分恢复,临床单独应用骨髓间充质干细胞移植治疗脊髓损伤安全有效,但临床效果不显著。进一步的研究表明,脊髓损伤后任何简单的介入策略都不能确保损伤传导束的再生和功能恢复。
创新要点:实验设计的自体周围神经与骨髓间充质干细胞联合移植治疗脊髓损伤,将国际前沿的干细胞技术与神经移植技术有机结合,采用手术与药物及物理相结合的治疗方案,综合考虑了脊髓损伤后继发损伤的防治、亚急性/慢性阶段的神经保护、轴索/神经元的持续再生以及神经回路的重建,以全新的角度、创新的思维来探索脊髓损伤的治疗。
偏倚或不足:本实验在临床上没有对照组,因为患者及家属都要求采用此方法帮助患者恢复。同时在临床上患者具有医疗知情权和选择治疗方法的权利,因此本文没有设对照组和单独的骨髓间充质干细胞和单独的外周神经移植组。
摘要
目的:研究发现,应用骨髓间充质干细胞联合周围神经移植治疗脊髓损伤有协同作用。实验拟验证自体骨髓间质干细胞联合周围神经移植治疗脊髓损伤的临床疗效,为脊髓损伤的治疗开辟新途径。
方法: 选择2003/2004河南省人民医院神经外科干细胞移植治疗中心收治的78例完全性脊髓损伤患者。男52例,女26例,年龄18~52岁。其中颈髓损伤12例,胸髓损伤46例,腰骶髓损伤20例,损伤1周至60个月。患者对治疗知情同意,并要求采用该方法治疗。无菌条件下,自患者髂前上棘及髂后上棘通过骨髓穿刺抽取骨髓,分离、纯化、培养骨髓间充质干细胞。选取患者自体腓肠神经作为周围神经移植供体,将自身腓肠神经应用显微外科方法去除外膜、束膜,并剪神经,使神经组织的质地、外观类似于马尾组织,将其排列呈多条状、纵行植入已切开的脊髓处或原囊肿腔内,然后用分离纯化的骨髓间充质干细胞移植焊接移植的神经,对患者行自体骨髓间充质干细胞联合周围神经移植治疗,术后给予神经生长因子等药物应用, 疗程为1个月,以促进损伤神经的修复。实验评估:通过电话随访和患者定时回医院复查的方式,术后每3个月随访1次,随访1年。术前、术后和随访按国际截瘫医学会评分标准ASIA评分标准评分,评分的增高表示患者的运动和感觉的功能的恢复。同时进行神经电生理、影像学等方面对比分析。
结果: 78例患者中除1例严重复合伤患者出现并发症,经积极治疗无效死亡,其余患者术后均顺利出院,原有症状改善情况,未出现明显不良毒副反应。患者术后ASIA评分的平均数较术前提高。37例出现运动、感觉、影像学、神经电生理方面的不同改善,25例出现不同程度的运动,感觉、神经电生理方面的改善,9例出现神经电生理方面的改善,6例无变化,1例死亡;在随后的1年随访中,除2例失访外,其余患者均有不同程度进一步恢复的趋势,无明显毒副反应发生。
结论: 自体骨髓间质干细胞联合周围神经移植治疗脊髓损伤促进脊髓损伤患者的功能恢复,安全有效,有临床推广应用的价值。
关键词: 移植;骨髓间充质干细胞;周围神经;脊髓损伤
李志营,步星耀,张圣旭,梁庆华,李太平,陈书连,李六一,赵耀武,翟亚平,张永福.自体骨髓间充质干细胞联合周围神经移植治疗脊髓损伤[J].中国组织工程研究与临床康复,2008,12(16):3041-3044
[www.zglckf.com/zglckf/ejournal/upfiles/08-16/16k-3041(ps).pdf]
河南省人民医院,
1神经外科,2骨科,3生物研究所,4肌电图室,5血液研究所,河南省郑州市 450003
李志营★,男,1981年生,河南省杞县人,汉族,新乡医学院在读硕士,主要从事脑、脊髓损伤的治疗研究。
xiangyu_16888@
163.com
通讯作者:步星耀,主任医师,博士后,研究生导师,河南省人民医院神经外科,河南省郑州市
450003 buxingyao@
126.com
河南省科技攻关项目(05244200
54)*与河南省医学科技攻关计划资助项目*
中图分类号: R394.2
文献标识码: A
文章编号: 1673-8225
(2008)16-03041-04
收稿日期:2007-12-05
修回日期:2008-01-16
(07-50-12-6748/GW·Q)
Autologous bone marrow mesenchymal stem cells in combination with peripheral nerve transplantation for treating spinal cord injury
Abstract
AIM: There are synergistic effects of bone marrow mesenchymal stem cells (BMSCs) combined with peripheral nerve transplantation for spinal cord injury (SCI). This article confirmed the therapeutic effect of BMSCs combining peripheral nerve transplantation on SCI. A new therapeutic method for SCI was authenticated.
METHODS: Totally 78 patients with complete SCI aged 18-52 years (52 males and 26 females) were enrolled at the Stem Cell Transplantation Center of Department of Neurosurgery of Henan People’s Hospital from 2003 to 2004. There were 12 patients with cervical cord injury, 46 patients with thoracic cord injury and 20 patients with lumbar sacral cord injury (injured for 1 week to 60 months). All patients singed informed consents. Bone marrow was sterilely collected from the anterior superior iliac spine and posterior superior iliac spine by bone marrow aspiration. BMSCs were harvested, purified and cultured. Autologous sural nerve was obtained from patients as donor for peripheral nerve transplantation. Adventitial coat of autologous sural nerve was removed, clustered and cut into cauda equina-like tissues, which were arranged stick-shape and longitudinally transplanted into the spinal cord or cystis. Patients received autologous BMSCs combined with peripheral nerve transplantation. These patients were treated with nerve growth factor after transplantation for one month to improve the restoration of injured nerve. Post-operative follow-up was performed by telephone or going back to hospital every three months, totally for 1 year. Preoperative and postoperative evaluation and follow-up were conducted according to International Medical Society of Paraplegia standards, American Spinal Injury Association (ASIA) scores, and the higher score represented the restoration of exercises and sensory function. Simultaneously, controlled analysis was done in imageology, and neural-electrophysiology.
RESULTS: All of the 78 patients were smoothly discharged except for 1 patient with serious compound wound died of complication after active treatment. Totally 77 patients were improved, and no obvious adverse events were found. Average ASIA score was higher after surgery than before surgery. Thirty-seven patients had improvement in motor, sensation, imageology and neural-electrophysiology. Twenty-five patients had improvement in motor, sensation and neural-electrophysiology. Nine patients had improvement in neural-electrophysiology. Six patients were ineffective. One patient died. In the one-year follow-up, two patients were dropped out, and the remaining was improved, and no obvious adverse events were found.
CONCLUSION: Peripheral nerve combining autologous BMSC transplantation can improve neural functional recovery of SCI patients. It is an effective and safe approach for treatment of SCI and worth to apply in clinic.
Li ZY, Bu XY, Zhang SX, Liang QH, Li TP, Chen SL, Li LY, Zhao YW, Zhai YP, Zhang YF.Autologous bone marrow mesenchymal stem cells in combination with peripheral nerve transplantation for treating spinal cord injury.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(16):3041-3044 [www.zglckf.com/zglckf/ejournal/upfiles/08-16/16k-3041(ps).pdf]
1Department of Neurosurgery, 2Department of Orthopaedics, 3Institute of Biology, 4Room of
Electromyogram, 5Institute of Haematology, Henan People’s Hospital, Zhengzhou 450003, Henan Province, China
Li Zhi-ying★, Studying for master’s degree, Department of Neurosurgery, Henan People’s Hospital, Zhengzhou 450003, Henan Province, China
xiangyu_16888@
163.com
Correspondence to: Bu Xing-yao, Chief physician, Doctor, Tutor of Post-graduate, Department of Neurosurgery, Henan People’s Hospital, Zhengzhou 450003, Henan Province, China
buxingyao@126.com
Supported by: the Tackle Key Program in Science and Technology of Henan Province, No.
0524420054*; a grant for Tackle Key Program in Medical Science and Technology of Henan
Province*
Received:2007-12-05
Accepted:2008-01-16
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