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Journal of Neurorestoratology  2019, Vol. 7 Issue (2): 70-81    doi: 10.26599/JNR.2019.9040008
Research Article     
Application of olfactory ensheathing cells in clinical treatment of spinal cord injury: meta-analysis and prospect
Huijing Chen1, Qijia Tan2, Caijun Xie2, Cong Li2, Yun Chen1, Yuer Deng1, Yanling Gan1, Wengang Zhan2, Zhiqiang Zhang2,(✉), Aruna Sharma3,(✉), Hari Sharma3,(✉)
1 The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
2 Guangzhou Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Guangzhou University of Chinese Medicine), Guangzhou, Guangdong, China
3 International Experimental CNS Injury & Repair (IECNSIR) University Hospital, Uppsala University, Uppsala, Sweden
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Abstract  Background:

A number of clinical trials of olfactory ensheathing cells (OECs) for the treatment of chronic spinal cord injury (SCI) have been carried out all over the world. However, their safety and efficacy have not been basically evaluated. Moreover, there are no uniform standards laid out for the use of optimal source, transplantation method and the dosage of OECs.

Objective:

This study evaluated the source, dose, and route of transplantation of OECs for the treatment of chronic SCI.

Methods:

PubMed, Cochrane Library, EMBASE, CNKI, and Wanfang Data were searched for the clinical studies of OECs in the treatment of chronic SCI on July 2018.

Results:

A total of 30 articles on OECs transplantation for chronic SCI were selected for comprehensive evaluation of OECs sources, doses, and transplantation methods. The efficacy of OECs in the treatment of chronic SCI was evaluated using Review Manager 5.3.

Conclusion:

Fetal OECs are the primary source of cells for the treatment of chronic SCI in OECs, with standardized cell-culture and quality-control processes. Fetal OECs can significantly improve the neurological function of patients with chronic SCI. It is an ideal cell therapy for neurorestoration. However to explore more precise and minimally invasive treatment options are required in the future.



Key wordsolfactory ensheathing cell (OEC)      spinal cord injury (SCI)      meta-analysis     
Received: 23 March 2019      Published: 22 July 2019
Corresponding Authors: Zhiqiang Zhang,Aruna Sharma,Hari Sharma   
Cite this article:

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. Journal of Neurorestoratology, 2019, 7: 70-81.

URL:

http://jnr.tsinghuajournals.com/10.26599/JNR.2019.9040008     OR     http://jnr.tsinghuajournals.com/Y2019/V7/I2/70

EMBASE
#1 'olfactory ensheathing cell'/exp OR 'ensheathing cells':ab,ti OR 'olfactory bulb cell':ab,ti OR 'Olfactory ensheathing glia':ab,ti OR 'ensheathing cell':ab,ti OR 'Olfactory Cortex cell':ab,ti OR 'olfactory cell':ab,ti OR 'olfactory bulb ensheathing cell line':ab,ti OR 'olfactory nerve ensheathing cells':ab,ti OR 'olfactory schwann cell':ab,ti OR 'schwann cells of the olfactory nerve':ab,ti OR 'OECs':ab,ti
#2 'spinal cord injury'/exp OR 'spinal cord trauma':ab,ti OR 'cord trauma, spinal':ab,ti OR 'cord traumas, spinal':ab,ti OR 'spinal cord traumas':ab,ti OR 'trauma, spinal cord':ab,ti OR 'traumas, spinal cord':ab,ti OR 'injuries, spinal cord':ab,ti OR 'cord injuries, spinal':ab,ti OR 'cord injury, spinal':ab,ti OR 'injury, spinal cord':ab,ti OR 'spinal cord injury':ab,ti OR 'myelopathy, traumatic':ab,ti OR 'myelopathies, traumatic':ab,ti OR 'traumatic myelopathies':ab,ti OR 'traumatic myelopathy':ab,ti OR 'spinal cord transection':ab,ti OR 'cord transection, spinal':ab,ti OR 'laceration, spinal cord':ab,ti OR 'lacerations, spinal cord':ab,ti OR 'spinal cord lacerations':ab,ti OR 'post-traumatic myelopathy':ab,ti OR 'myelopathies, post-traumatic':ab,ti OR 'myelopathy, post-traumatic':ab,ti OR 'post-traumatic myelopathies':ab,ti OR 'spinal cord contusion':ab,ti OR 'contusion, spinal cord':ab,ti OR 'contusions, spinal cord':ab,ti OR 'cord contusion, spinal':ab,ti OR 'cord contusions, spinal':ab,ti OR 'spinal cord contusions':ab,ti OR 'injured spinal cord':ab,ti OR 'spinal cord hemisection':ab,ti OR 'spinal compression':ab,ti
#3 'human':ab,ti OR 'patients':ab,ti
#1 AND #2 AND #3
Cochrane Library
#1 MeSH descriptor: [Spinal Cord Injuries] explode all trees
#2 Spinal Cord Trauma:ti,ab,kw or Myelopathy, Traumatic:ti,ab,kw or Spinal Cord Transection:ti,ab,kw or Spinal Cord Laceration:ti,ab,kw or Post-Traumatic Myelopathy:ti,ab,kw (Word variations have been searched)
#3 #1 AND #2
#4 olfactory ensheathing cell:ti,ab,kw or olfactory bulb cell:ti,ab,kw or Olfactory ensheathing glia:ti,ab,kw or olfactory schwann cell:ti,ab,kw or OECs:ti,ab,kw (Word variations have been searched)
#5 #3 and #4
PubMed
Search olfactory ensheathing cell[Title/Abstract]) OR ensheathing cells[Title/Abstract]) OR olfactory bulb cell[Title/Abstract]) OR Olfactory ensheathing glia[Title/Abstract]) OR ensheathing cell[Title/Abstract]) OR Olfactory Cortex cell[Title/Abstract]) OR olfactory cell[Title/Abstract]) OR olfactory bulb ensheathing cell line[Title/Abstract]) OR olfactory nerve ensheathing cells[Title/Abstract]) OR olfactory schwann cell[Title/Abstract]) OR schwann cells of the olfactory nerve[Title/Abstract]) OR OECs[Title/Abstract]) AND (("Spinal Cord Injuries"[Mesh]) OR Spinal Cord Trauma[Title/Abstract]) OR Cord Trauma, Spinal[Title/Abstract]) OR Cord Traumas, Spinal[Title/ Abstract]) OR Spinal Cord Traumas[Title/Abstract]) OR Trauma, Spinal Cord[Title/Abstract]) OR Traumas, Spinal Cord[Title/Abstract]) OR Injuries, Spinal Cord[Title/Abstract]) OR Cord Injuries, Spinal[Title/Abstract]) OR Cord Injury, Spinal[Title/Abstract]) OR Injury, Spinal Cord[Title/Abstract]) OR Spinal Cord Injury[Title/Abstract]) OR Myelopathy, Traumatic[Title/Abstract]) OR Myelopathies, Traumatic[Title/Abstract]) OR Traumatic Myelopathies[Title/Abstract]) OR Traumatic Myelopathy[Title/Abstract]) OR Spinal Cord Transection[Title/Abstract]) OR Cord Transection, Spinal[Title/Abstract]) OR Cord Transections, Spinal[Title/Abstract]) OR Spinal Cord Transections[Title/Abstract]) OR Transection, Spinal Cord[Title/Abstract]) OR Transections, Spinal Cord[Title/Abstract]) OR Spinal Cord Laceration[Title/Abstract]) OR Cord Laceration, Spinal[Title/Abstract]) OR Cord Lacerations, Spinal[Title/Abstract]) OR Laceration, Spinal Cord[Title/Abstract]) OR Lacerations, Spinal Cord[Title/Abstract]) OR Spinal Cord Lacerations[Title/Abstract]) OR Post-Traumatic Myelopathy[Title/Abstract]) OR Myelopathies, Post-Traumatic[Title/Abstract]) OR Myelopathy, Post-Traumatic[Title/Abstract]) OR Post Traumatic Myelopathy[Title/Abstract]) OR Post-Traumatic Myelopathies[Title/Abstract]) OR Spinal Cord Contusion[Title/Abstract]) OR Contusion, Spinal Cord[Title/Abstract]) OR Contusions, Spinal Cord[Title/Abstract]) OR Cord Contusion, Spinal[Title/Abstract]) OR Cord Contusions, Spinal[Title/Abstract]) OR Spinal Cord Contusions[Title/Abstract]) OR Injured spinal cord[Title/Abstract]) OR Spinal cord Hemisection[Title/Abstract]) OR Spinal compression[Title/Abstract]) AND ((human[Title/Abstract]) OR patients[Title/Abstract])
Table 1Keywords of EMBASE, Cochrane Library and PubMed.
Fig. 1Literature publication trend chart.
ReferenceSourceInjection siteDoseVolume, points
Wu, J et al. [12]fetal OECsrostral and caudal ends of the lesions5 × 10525 μL/point, 2
Zhang, Z C et al. [13]
Zhang, L et al. [14]fetal OECsGroup A:the border of the superior part of lesions and normal spinal cord Group B: the either sites of the lesionsNAGroup A: 50 μL/point, 1 Group B: 50 μL/ 2~4 points, 2~5
Liu, C et al. [15]fetal OECsthe border of lesions and normal spinal cord106100 μL (total), multiple
Zheng, Z C et al. [16,17,18]fetal OECsupper or lower injured region and left or right normal spinal cord(1~4) × 10650 μL/2~5 points, 2~5
Huang, H et al. [19,20,21,22,23,24,25,26]fetal OECsrostral and caudal ends of the lesion10625 μL/point, 2
Chen, L et al. [11,27,28]
Dong, W et al. [29]fetal OECsboth posterior horns of spinal cord 0.5 cm distal and proximal to SCI area8 × 10510 μL/point, 4
Bao, G F et al. [30]fetal OECsmultiple points of the cross between spinal cord injury and normal spinal cord5 × 10525 μL (total), multiple
Rao, Y et al. [31]fetal OECsthe border between lesions and normal spinal cord(2~5) × 10650 μL/2~5 points, 2~5
Rao, Y et al. [32]autologous OECslocal anesthesia, MR-guided injection to the lesion tail8 × 1072 mL/6 points*, 6
Rao, Y et al. [33]autologous OECsthe border between lesions and normal spinal cord2 × 10640~50 μL/4~5 points, 4~5
Lima, C et al. [34,35]OMAsparenchymaNANA
Feron, F et al. [36]autologous OECsMatrix 1(1.2~2.8) × 1081.1 μL, 270~630
Mackay-Sim, A et al. [37]
Tabakow, P et al. [38]autologous OECs+ONFsMatrix 21.8 × 106~ 2.12 × 10760~106 μL/ 20~46 points, 20~46
Table 2Features of included studies.
Author ,YearOperation timeSample sizeSCI to implantFollow upObject selectionCom parabilityResult evaluationScore
ABCDEFGH
Wu, J et al., 2012 [12]1/2004?12/2004116~42 months12~18 months001110115
Zheng, Z C et al., 2008 [17]6/2004?6/2007114> 6 months2~4 weeks111110016
Zheng, Z C et al., 2013 [18]7/2009?7/201043> 6 months3~8 weeks111110016
Huang, H et al., 2006 [23]11/2001?1/20043006 months~ 18 years2~8 weeks111110016
Huang, H et al., 2012 [22]*NA108NA3.47 ± 1.12 years111110117
Dong, W et al., 2013 [29]9/2005–3/201024> 6 monthsaverage of 3.2 years001110115
Table 3Fetal OECs efficacy evaluation literature and document quality evaluation.
Fig. 2Short-term ASIA score of motor (A), light touch (B) and pinprick (C). (1) Complete paraplegia group; (2) incomplete paralysis group; (3)injured for 6 months to 2 years; (4) injured for > 2 years.
Fig. 3Long-term ASIA score of motor (A), light touch (B) and pinprick (C). (1) Complete paraplegic group; (2) incomplete paralysis group; (3) foreign group; (4) good domestic rehabilitation group; (5) poor domestic rehabilitation group.
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