Please wait a minute...
Journal of Neurorestoratology  2021, Vol. 9 Issue (2): 94-105    doi: 10.26599/JNR.2021.9040008
Research Article     
Olfactory ensheathing cell transplantation for chronic spinal cord injury: A long-term follow-up study
Naifeng Kuang1,Xiaoyu Wang1,Yuexia Chen1,Guifeng Liu1,Fan’e Kong2,Nan Wang2,Rui Feng2,Yan Wang1,Xiaojing Du1,Zuncheng Zheng1,(✉)()
1Department of Rehabilitation, Taian City Central Hospital, Taian 271000, Shandong, China
2Shandong First Medical University & Shandong Academy of Medical Science, Taian 271016, Shandong, China
Download: PDF (984 KB)      HTML
Export: BibTeX | EndNote (RIS)      

Abstract  

Spinal cord injury is a serious disabling condition. Transplantation of olfactory ensheathing cells (OECs) is one of the most promising treatments for spinal cord injury (SCI). Thirty-nine patients with chronic SCI received OEC transplantation and completed long-term follow-up, with a minimum follow-up of 7 years. We assessed sensorimotor function with the American Spinal Injury Association (ASIA) Impairment Scale (AIS) and autonomic nervous function by the International Standards to document remaining Autonomic Function after Spinal Cord Injury (ISAFSCI), and sympathetic skin responses (SSR). The scores of each group were significantly higher after OECs transplantation than before treatment. SSR latencies were shorter and response amplitudes increased after treatment. Long-term follow-up showed further improvement only in motor function and autonomic function compared with 3 months postoperatively. No complications occurred in any patient during long-term follow-up. The results indicate that the transplantation of OECs in spinal cord restored function without serious side effects.



Key wordschronic spinal cord injury      olfactory ensheathing cell transplantation      safety      efficacy     
Received: 28 April 2021      Published: 19 October 2021
Fund:  Shandong Provincial Natural Science Foundation of China(ZR2014HM046);Medicine and Health Care Science & Technology Development Programme of Shandong Province(2015WS0120);Taian City Technology Development Program(2019NS211);The presented research was financially supported by Shandong Provincial Natural Science Foundation of China (Grant Nos. ZR2014HM046, ZR2017PH031, and ZR2014 HL101), Medicine and Health Care Science & Technology Development Programme of Shandong Province (Grant Nos. 2015WS0120, 202020010731), and Taian City Technology Development Program (Grant Nos. 2019NS211, 2019NS163).
Corresponding Authors: Zuncheng Zheng     E-mail: zxyyzhengzuncheng@126.com
Cite this article:

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. Journal of Neurorestoratology, 2021, 9: 94-105.

URL:

http://jnr.tsinghuajournals.com/10.26599/JNR.2021.9040008     OR     http://jnr.tsinghuajournals.com/Y2021/V9/I2/94

CharacteristicsDescriptionnPercentage
SexMale3897.44%
Female12.56%
Type of injuryComplete1641.03%
Incomplete2358.97%
Level of injuryCervical1333.33%
Thoracic2358.97%
Lumbar37.69%
ASIA categoryA1435.90%
B1743.59%
C37.69%
D512.82%
Type of catheter on admissionIFC512.82%
SPC12.56%
CIC3384.62%
Without catheter00
Type of catheter at follow upIFC00
SPC12.56%
CIC3384.62%
Without catheter512.82%
Table 1Demographic and clinical characteristics of the patients.
Preoperative 1 dayPostoperative 3 monthsFollow-upP*P**P***
Motor50.92 ± 16.3554.85 ± 17.1656.62 ± 17.670.000.000.00
Light Touch63.08 ± 22.6366.15 ± 22.5966.03 ± 22.480.000.000.91
Pin Prick62.92 ± 22.6166.59 ± 22.9066.21 ± 22.720.000.000.33
Table 2Comparison of patients scores by AIS.
PreoperativePostoperative 3 monthsFollow-upP*P**P***
GAF6.46 ± 2.7238.82 ± 1.5549.05 ± 1.4500.000.000.14
LUT, bowel and sexual11.23 ± 3.28012.49 ± 4.77712.59 ± 4.8640.000.000.01
Table 3Comparison of patients scores by ISAFSCI.
Motor Light touch Pin prick GAF LUT, bowel and sexual
3-pre7-pre3-pre7-pre3-pre7-pre3-pre7-pre3-pre7-pre
Complete SCI1.92 ± 0.491.92 ± 0.491.7 ± 0.441.62 ± 0.411.88 ± 0.481.45 ± 0.372.32 ± 0.62.57 ± 0.663.68 ± 0.953.94 ± 1.01
Incomplete SCI2.1 ± 0.423.09 ± 0.632.05 ± 0.412.19 ± 0.441.99 ± 0.41.97 ± 0.41.92 ± 0.392.01 ± 0.412.64 ± 0.533.07 ± 0.62
p-value0.020.000.720.970.620.260.240.150.030.02
Table 4The differences in AIS and ISAFSCI scores of complete and incomplete SCI.
PreoperativePostoperative 3 monthsFollow-upP*P**P***
Lat (ms)2323.19 ± 1330.131604.64 ± 280.14785.23 ± 432.520.150.010.00
Ampl (μV)149.43 ± 64.54288.94 ± 115.70831.80 ± 189.700.010.000.00
Table 5Quantitative SSR parameters in SCI patients before and after treatment
DescriptionnPercentage
Complications on admissionFever00
Infection25.13%
Neuropathic pain410.26%
Decubitus410.26%
Autonomic dysfunction25.13%
Postoperative complicationsFever1128.21%
Infection00
Cerebral spinal fluid leaks12.56%
Operative incision of healing25.13%
Neuropathic pain410.26%
Complications at dischargeFever00
Infection00
Cerebral spinal fluid leaks00
Operative incision of healing00
Neuropathic pain410.26%
Complications during follow-upTumor00
Cyst formation00
Abscess00.00%
Neuropathic pain410.26%
Table 6Complication in SCI patients before and after treatment.
Fig. 1Example images of the follow-up MRI. (A) MRI of a patient with T10 SCI 9 years postoperatively. (B) MRI of a patient with L2 SCI 7 years postoperatively.
[1]   Lee BB, Cripps RA, Fitzharris M, et al. The global map for traumatic spinal cord injury epidemiology: update 2011, global incidence rate. Spinal Cord 2014, 52(2): 110-116.
[2]   Tran AP, Silver J. Neuroscience. Systemically treating spinal cord injury. Science 2015, 348(6232): 285-286.
[3]   Huang H, Chen L, Mao G, et al. The 2019 yearbook of Neurorestoratology. J Neurorestoratol 2020, 8(1): 1-11.
[4]   Huang HY, Sharma HS, Chen L, et al. Review of clinical neurorestorative strategies for spinal cord injury: Exploring history and latest progresses. J Neurorestoratol 2018, 6(1): 171-178.
[5]   Targeting pain of spinal-cord injury. Nature 2016, 537(7622): 588.
[6]   Rao YJ, Zhu WX, Guo YX, et al. Long-term outcome of olfactory ensheathing cell transplantation in six patients with chronic complete spinal cord injury. Cell Transplant 2013, 22(): S21-S25.
[7]   Huang HY, Xi HT, 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.
[8]   Zheng ZC, Liu GF, Chen YX, et al. Olfactory ensheathing cell transplantation improves sympathetic skin responses in chronic spinal cord injury. Neural Regen Res 2013, 8(30): 2849-2855.
[9]   Huang H, Gao W, Yan Z, et al. Standards of clinical-grade olfactory ensheathing cell culture and quality control (2020 China Version). J Neurorestoratol 2020, 8(4): 217-231.
[10]   Krassioukov A, Biering-S?rensen F, Donovan W, et al. International standards to document remaining autonomic function after spinal cord injury. J Spinal Cord Med 2012, 35(4): 201-210.
[11]   Féron F, Perry C, Cochrane J, et al. Autologous olfactory ensheathing cell transplantation in human spinal cord injury. Brain 2005, 128(Pt 12): 2951-2960.
[12]   Mackay-Sim A, Féron F, Cochrane J, et al. Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial. Brain 2008, 131(pt 9): 2376-2386.
[13]   Wu J, Sun TS, Ye CQ, et al. Clinical observation of fetal olfactory ensheathing glia transplantation (OEGT) in patients with complete chronic spinal cord injury. Cell Transplant 2012, 21(): S33-S37.
[14]   Cobb J, Dumont FS, Leblond J, et al. An exploratory analysis of the potential association between SCI secondary health conditions and daily activities. Top Spinal Cord Inj Rehabil 2014, 20(4): 277-288.
[15]   Alexander MS, Biering-Sorensen F, Bodner D, et al. International standards to document remaining autonomic function after spinal cord injury. Spinal Cord 2009, 47(1): 36-43.
[16]   Squair JW, le Nobel G, Noonan VK, et al. Assessment of clinical adherence to the international autonomic standards following spinal cord injury. Spinal Cord 2015, 53(9): 668-672.
[17]   Margaritella N, Mendozzi L, Garegnani M, et al. Sympathetic skin response in multiple sclerosis: a meta-analysis of case-control studies. Neurol Sci 2018, 39(1): 45-52.
[18]   Ke JQ, Shao SM, Zheng YY, et al. Sympathetic skin response and heart rate variability in predicting autonomic disorders in patients with Parkinson disease. Medicine (Baltimore) 2017, 96(18): e6523.
[19]   Hanson P, Prévinaire JG, Soler JM, et al. Sympathetic skin response in spinal cord injured patients: preliminary report. Electromyogr Clin Neurophysiol 1992, 32(10/11): 555-557.
[20]   Curt A, Weinhardt C, Dietz V. Significance of sympathetic skin response in the assessment of autonomic failure in patients with spinal cord injury. J Auton Nerv Syst 1996, 61(2): 175-180.
[21]   Zhang ZR, Wang FY, Song MJ. The cell repair research of spinal cord injury: a review of cell transplantation to treat spinal cord injury. J Neurorestoratol 2019, 7(2): 55-62.
[1] Feng Zhang, Xiangzhi Meng, Fang Lu, Aixian Liu, Hongyun Huang. Olfactory ensheathing cell transplantation for a patient with chronic sciatic nerve injury[J]. Journal of Neurorestoratology, 2017, 5(1): 1-4.
[2] Xiang Li, Guangsheng Li, Keith Dip-Kei Luk, Yong Hu. Neurorestoratology evidence in an animal model with cervical spondylotic myelopathy[J]. Journal of Neurorestoratology, 2017, 5(1): 21-29.