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Journal of Neurorestoratology  2021, Vol. 9 Issue (2): 106-116    doi: 10.26599/JNR.2021.9040009
Research Article     
Ten years of clinical observation of olfactory ensheathing cell transplantation in patients with spinal cord injury
Zhijian Cheng1,Rui Wang1,2,Kai Cao1,Guoyu Wang1,Jie Qin1,Haopeng Li1,Jiaxi Li1,Dong Wang1,(✉)(),Xijing He1,3,(✉)()
1Second Department of Orthopedics, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi, China
2Department of Orthopaedics, Postdoctoral Research Center, Xi’an Gaoxin Hospital, Xi'an 710075, Shaanxi, China
3Xi’an International Medical Center Hospital, Xi’an 710100, Shaanxi, China
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Abstract  Objective:

To evaluate the long-term curative efficacy and safety of olfactory ensheathing cell (OEC) transplantation by 10 years of follow-up investigation.

Methods:

A follow-up observation was done on 13 patients with allograft olfactory bulb-derived OEC transplantation from September 2005 to September 2007 at the Second Affiliated Hospital of Xi’an Jiaotong University. After cell purification, amplification, and identification, a 2 × 107/mL cell suspension was prepared for transplantation. In the posterior horn of the spinal cord 0.5 cm distal and proximal to the spinal cord injury zone, 4 needle points were selected to avoid the blood vessels. The needle depth was 3 mm, and the injection volume per point was 10 μL. Postoperatively and at 1 week, 4 weeks, 12 weeks, 24 weeks, 1 year, 3 years, 5 years, and 10 years after the surgery, the patient’s American Spinal Injury Association (ASIA) score, adverse reactions, and other minor observations were assessed.

Results:

All the patients did not have serious complications. No gliomas or other new organisms formed during the 10-year observation period. Eight of 13 patients had improvement in sensory function, and 5 patients showed improvement in motor function. The ASIA acupuncture, light touch, and exercise scores improved significantly 1 year after the surgery, and this improvement continued until the 10-year follow-up period. Three of 13 patients had improvement in defecation and urination, and 1 patient had improved neuralgia after spinal cord injury.

Conclusion:

OEC transplantation is safe and effective in treating spinal cord injury. The observation period of OEC transplantation is 1 to 3 years.



Key wordsspinal cord injury      olfactory ensheathing cells      cell transplantation      clinical observation      retrospective analysis     
Received: 09 May 2021      Published: 19 October 2021
Fund:  National Natural Science Foundation of China(81801237);National Key Research and Development Project of the People′s Republic of China(2018YFE0114200);This work was supported by National Natural Science Foundation of China (Grant No. 81801237), and National Key Research and Development Project of the People′s Republic of China (Grant No. 2018YFE0114200).
Corresponding Authors: Dong Wang,Xijing He     E-mail: wado110@163.com;xijing_h@vip.tom.com
Cite this article:

Zhijian Cheng,Rui Wang,Kai Cao,Guoyu Wang,Jie Qin,Haopeng Li,Jiaxi Li,Dong Wang,Xijing He. Ten years of clinical observation of olfactory ensheathing cell transplantation in patients with spinal cord injury. Journal of Neurorestoratology, 2021, 9: 106-116.

URL:

http://jnr.tsinghuajournals.com/10.26599/JNR.2021.9040009     OR     http://jnr.tsinghuajournals.com/Y2021/V9/I2/106

Fig. 1Characterization of OECs in vitro. (A) Phase of OECs. (B) Immunofluorescent staining of the OEC marker p75 (red). Nuclei in (B) were stained with 4′,6-diamidino-2-phenylindole (blue). Scale bar = 200 μm.
Fig. 2Schematic diagram of OEC transplantation.
PreoperativePostoperative
1 day1 week4 weeks12 weeks24 weeks1 year3 years5 years10 years
Motor40.8 ± 9.240.1 ± 9.441.1 ± 8.941.1 ± 8.941.3 ± 9.141.2 ± 9.041.7 ± 8.841.7 ± 8.641.7 ± 8.841.5 ± 8.9
Pinprick42.4 ± 14.042.6 ± 13.744.5 ± 13.944.3 ± 13.844.8 ± 13.545.3 ± 13.045.5 ± 12.845.5 ± 13.045.6 ± 12.945.5 ± 13.0
Light touch41.5 ± 15.441.7 ± 15.442.5 ± 15.242.8 ± 15.142.9 ± 15.343.2 ± 15.243.4 ± 15.343.5 ± 15.243.6 ± 15.343.5 ± 15.2
Table 1ASIA scores of patients receiving OEC transplantation at different observation time points.
No.SensoryMotorBladder and bowel functionSelf-evaluation
1YesYesYesYes
2YesNoNoYes
3NoNoNoNo
4YesNoYesYes
5YesYesYesYes
6NoNoNoNo
7YesYesNoYes
8YesYesNoYes
9NoNoNoNo
10NoNoNoNo
11YesNoNoYes
12YesYesNoYes
13NoNoNoNo
Table 2Comparison of patients’ improvement preoperatively and postoperatively.
[1]   Li Y, Field PM, Raisman G. Repair of adult rat corticospinal tract by transplants of olfactory ensheathing cells. Science 1997, 277(5334): 2000-2002.
[2]   Watzlawick R, Rind J, Sena ES, et al. Olfactory ensheathing cell transplantation in experimental spinal cord injury: effect size and reporting bias of 62 experimental treatments: a systematic review and meta-analysis. PLoS Biol 2016, 14(5): e1002468.
[3]   Li L, Adnan H, Xu B, et al. Effects of transplantation of olfactory ensheathing cells in chronic spinal cord injury: a systematic review and meta-analysis. Eur Spine J 2015, 24(5): 919-930.
[4]   Lima C, Pratas-Vital J, Escada P, et al. Olfactory mucosa autografts in human spinal cord injury: a pilot clinical study. J Spinal Cord Med 2006, 29(3): 191-203; discussion 204.
[5]   Huang H, Xi H, Chen L, et al. Long-term outcome of olfactory ensheathing cell therapy for patients with complete chronic spinal cord injury. Cell Transplant 2012, 21(): S23-S31.
[6]   Moviglia GA, Fernandez Vi?a R, Brizuela JA, et al. Combined protocol of cell therapy for chronic spinal cord injury. Report on the electrical and functional recovery of two patients. Cytotherapy 2006, 8(3): 202-209.
[7]   Beijing declaration of international association of neurorestoratology (IANR). Cell Transplant 2009, 18(4): 487.
[8]   Pascual JI, Gudi?o-Cabrera G, Insausti R, et al. Spinal implants of olfactory ensheathing cells promote axon regeneration and bladder activity after bilateral lumbosacral dorsal rhizotomy in the adult rat. J Urol 2002, 167(3): 1522-1526.
[9]   Lang BC, Zhang Z, Lv LY, et al. OECs transplantation results in neuropathic pain associated with BDNF regulating ERK activity in rats following cord hemisection. BMC Neurosci 2013, 14: 80.
[10]   Luo Y, Zou Y, Yang LH, et al. Transplantation of NSCs with OECs alleviates neuropathic pain associated with NGF downregulation in rats following spinal cord injury. Neurosci Lett 2013, 549: 103-108.
[1] Naifeng Kuang,Xiaoyu Wang,Yuexia Chen,Guifeng Liu,Fan’e Kong,Nan Wang,Rui Feng,Yan Wang,Xiaojing Du,Zuncheng Zheng. Olfactory ensheathing cell transplantation for chronic spinal cord injury: A long-term follow-up study[J]. Journal of Neurorestoratology, 2021, 9(2): 94-105.
[2] Xiaodong Guo, Yaping Feng, Tiansheng Sun, Shiqing Feng, Jiaguang Tang, Lin Chen, Xiaojian Cao, Haodong Lin, Xijing He, Meihua Li, Zhicheng Zhang, Guoyong Yin, Xifan Mei, Hongyun Huang. Clinical guidelines for neurorestorative therapies in spinal cord injury (2021 China version)[J]. Journal of Neurorestoratology, 2021, 9(1): 31-49.
[3] Yunliang Wang, Xiaoling Guo, Jun Liu, Zuncheng Zheng, Ying Liu, Wenyong Gao, Juan Xiao, Yanqiu Liu, Yan Li, Manli Tang, Linlin Wang, Lin Chen, Di Chen, Deqiang Guo, Fei Liu, Weidong Chen, Baomin Chan, Bo Zhou, Aibing Liu, Gengsheng Mao, Hongyun Huang. Olfactory ensheathing cells in chronic ischemic stroke: A phase 2, double-blind, randomized, controlled trial[J]. Journal of Neurorestoratology, 2020, 8(3): 182-193.
[4] Chao Chen, Qingfa Chen, Yan Liu, Chongyang Zhang, Kaixiang Zhu, Xue Li, Haitao Xie, Rui Zhang. The cell repair research for Parkinson’s disease: A systematic review[J]. Journal of Neurorestoratology, 2020, 8(2): 93-103.
[5] Hongyun Huang, Lin Chen, Gengsheng Mao, Hari Shanker Sharma. Clinical neurorestorative cell therapies: Developmental process, current state and future prospective[J]. Journal of Neurorestoratology, 2020, 8(2): 61-82.
[6] Miaomiao Zhuang, Qingheng Wu, Feng Wan, Yong Hu. State-of-the-art non-invasive brain–computer interface for neural rehabilitation: A review[J]. Journal of Neurorestoratology, 2020, 8(1): 12-25.
[7] Changke Ma, Peng Zhang, Yixin Shen. Progress in research into spinal cord injury repair: Tissue engineering scaffolds and cell transdifferentiation[J]. Journal of Neurorestoratology, 2019, 7(4): 196-206.
[8] Wenbin Ding , Shaocheng Zhang, Dajiang Wu , Yanpeng Zhang , Hualong Ye. Hand function reconstruction in patients with chronic incomplete lower cervical spinal cord injury by nerve segment insert grafting: a preliminary clinical report[J]. Journal of Neurorestoratology, 2019, 7(3): 129-135.
[9] Zhenrong Zhang, Fangyong Wang, Mingjie Song. The cell repair research of spinal cord injury: a review of cell transplantation to treat spinal cord injury[J]. Journal of Neurorestoratology, 2019, 7(2): 55-62.
[10] Huijing Chen, Qijia Tan, Caijun Xie, Cong Li, Yun Chen, Yuer Deng, Yanling Gan, Wengang Zhan, Zhiqiang Zhang, Aruna Sharma, Hari Sharma. Application of olfactory ensheathing cells in clinical treatment of spinal cord injury: meta-analysis and prospect[J]. Journal of Neurorestoratology, 2019, 7(2): 70-81.
[11] Yi Kang, Han Ding, Hengxing Zhou, Zhijian Wei, Lu Liu, Dayu Pan, Shiqing Feng. Epidemiology of worldwide spinal cord injury: a literature review[J]. Journal of Neurorestoratology, 2018, 6(1): 1-9.
[12] Zhongju Shi, Zhijian Wei, Shiqing Feng, Gustavo Moviglia, Lin Chen, Ping Wu. Highlights for the 10th Annual Conference of the International Association of Neurorestoratology[J]. Journal of Neurorestoratology, 2018, 6(1): 84-87.
[13] Andrey S. Bryukhovetskiy. Translational experience of 28 years of use of the technologies of regenerative medicine to treat complex consequences of the brain and spinal cord trauma: Results, problems and conclusions[J]. Journal of Neurorestoratology, 2018, 6(1): 99-114.
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[15] Gustavo A. Moviglia, M. Teresita Moviglia Brandolino, Damián Couto, Samanta Piccone. Local immunomodulation and muscle progenitor cells induce recovery in atrophied muscles in spinal cord injury patients[J]. Journal of Neurorestoratology, 2018, 6(1): 136-145.