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Journal of Neurorestoratology  2018, Vol. 6 Issue (1): 146-151    doi: 10.26599/JNR.2018.9040012
Review Article     
Comparison of intramedullary transplantation of olfactory ensheathing cell for patients with chronic complete spinal cord injury worldwide
Lin Chen1, Yuqi Zhang2,(✉), Xijing He3, Saberi Hooshang4
1 Department of Neurorestoratology, Yuquan Hospital, Tsinghua University, Beijing, China
2 Department of Neurosurgery, Yuquan Hospital, Tsinghua University, Beijing, China
3 Department of Orthopaedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi’an, China
4 Brain and Spinal cord Injury Research Center (BASIR), Neuroscience Institute, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
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Abstract  Objectives:

Traumatic spinal cord injury (tSCI) remains a major clinical challenge. Cell transplantation brings a glimmer of light, among them olfactory ensheathing cells (OECs) have shown some neurorestorative effect. Due to the results of each group lack basic consistency, many technical details are believed to affect the overall outcome. We compare the clinical outcome of intramedullary transplant of olfactory ensheathing cells for patients with spinal cord injury at multi-centers worldwide, and to explore the potential standardized transplantation that suits for the clinical requirements.

Methods:

Here, we used the Pubmed and CNKI databases to search online the literatures published in the last 20 years for the clinical studies/trials of OECs for chronic spinal cord injury in the representative clinical center. The results of these representative clinical treatment centers were searched and analyzed. The parameters which may affect the effect including the concentration of cells, the total number of cells, the choice of incision, the site of transplantation, the number of transplantation sites, the advantages and disadvantages of transplantation equipment, and postoperative management, were compared carefully to clarify its impact on the clinical results.

Results:

In these literatures, 2 Chinese centers, 1 Australian center and 1 European center were selected for intraspinal transplantation. The reason of different results may be due to the excessive injection times and/or the excessive total injection volume.

Conclusions:

Cell implant to the spinal cord parenchyma is effective for restoring neurological functions, but improper procedures may lead to ineffective results. Concise surgery appears to be more suitable for clinical application than ostensibly precise and complex injection procedures. Sufficient rehabilitation training is surely necessary for the integration of motor recovery after cell transplantation.



Key wordsspinal cord injury      olfactory ensheathing cell      neurorestoration cell transplantation     
Received: 06 December 2018      Published: 30 December 2018
Corresponding Authors: Yuqi Zhang   
Cite this article:

Lin Chen, Yuqi Zhang, Xijing He, Saberi Hooshang. Comparison of intramedullary transplantation of olfactory ensheathing cell for patients with chronic complete spinal cord injury worldwide. Journal of Neurorestoratology, 2018, 6: 146-151.

URL:

http://jnr.tsinghuajournals.com/10.26599/JNR.2018.9040012     OR     http://jnr.tsinghuajournals.com/Y2018/V6/I1/146

AuthorNationYearCase (n)Cell typeRoute of transplant
Huang H, et al.China2003171OECcord parenchyma
Rabinovich SS, et al.Russia200315hemopoietic tissues+OECsubarachnoidally
Féron F, et al.Australia20053OECcord parenchyma
Guest J, et al.United States20061OECcord parenchyma
Lima C, et al.Portugal20067olfactory mucosacord parenchyma
Huang H, et al.China2006222OECcord parenchyma
Mackay-Sim A, et al.Australia20086OECcord parenchyma
Lima C, et al.Portugal201020olfactory mucosal autograftscord parenchyma
Zheng ZC, et al.China2010213OECcord parenchyma
Huang H, et al.China2012108OECcord parenchyma
Wu J, et al.China201211OECcord parenchyma
Wang D, et al.China201224OECcord parenchyma
Rao Y, et al.China20138OECcord parenchyma
Tabakow P, et al.Poland+UK20136autologous mucosal olfactoryensheath ing cells and olfactory nerve fibroblastscord parenchyma
Table 1List of selected clinical studies on olfactory ensheathing cell transplantation for treatment of chronic complete spinal cord injury.
AuthorCase (n)Incision sizeTransplant siteCell concen trationTotal amount of cellsTransplant deviceAverage operation timePostoperative managementFollow-up timeComplicationClinical efficacy
Huang H, et al. [7]1714 cmThe upper and lower boundary areas of the damaged area and the normal area, 2-4 injection points10,000 single cells /μL500,000 cells / 50 μL4.5# syringe needle (approved by the Food and Drug Admini stration)1.5 hPostoperative rehabilitation training2–8 weeksNo serious complicationsImproved
Wang D, et al. [11]244–6 cmSpinal gray matter at a distance of 0.5 cm from the distal and proximal ends of the spinal cord injury zone, 4 injection points10,000/μL500,000/40 μL5# syringe needle (approved by the Food and Drug Admini stration)1.7 h (1.5 – 2.5 h)Postoperative rehabilitation training3.2 yr (0.5−5.2 yr)No serious complicationsNine of the 10 patients had a 1 to 2 spinal cord segment with a sensory level of injury. There was no change in motor function. There was no change in the sensory level of injury in 1 patient, but his limb spasm was significantly relieved after surgery.
Féron F and Mackay-Sim A, et al. [15,16]34–6 cm1μL per injec tions, spinal cord injury zone, one ver tebral body segment at the distal end and the proximal end. number of injection points: Case 1: 270Case 2: 545Case 3: 63080,000 cells/μLPatient 1 297μl (12 million) Patient 2 599.5μl (24 million) Patient 1 693μl (28 million)Self-made microinjection instruments4 hPostoperative rehabilitation training3 yrNo serious complicationsIn 1# patients, touch and pinprick improved on both sides of the body, decreased more than 3 dermatodes
Tabakow P, et al. [14]36–8 cmSpinal cord injury zone, one vertebral body segment at the distal and proxi mal ends, 0.5 μl per injections, Case 1: 20 sites (120 injections), case 2: 40 sites (128 injections), case 3: 46 sites (212 injections)30,000–200,000 cells/μLCase 1: 60 μL (1,800,000), Case 2: 64 μL (1,920,000), Case 3: 106 μL (21,200,000)Self-made microinjection instruments9–11 hPostoperative rehabilitation training1 yrLong-term no complications. Recent com plications include: fever (T1, T2, T3) Urinary tract infec tion (T1, T2) Mild anemia (T1, T2) Anemia requiring blood transfusion (T3) Systemic hypo tension (T3) Pressure sore ulcer (T1) Temporary loss of musculocutaneous nerve (T1)The first 2 surgical patients ASIA A to ASIA C and ASIA B. Diffusion tensor imaging showed that the spinal cord injury in these patients focused on the continuity of some white matter bundles throughout the process. The third surgical patient, although maintaining ASIA A, showed a segment of motion and sensory function below the degree of injury. Neurophysiological examination showed improvement in spinal cord conduc tion and lower limb muscle activity.
Huang H, et al. [10]108 (79 cases in rehabili tation group; 29 cases in poor rehabili tation training)2–3 cm keyhole surgeryThe upper and lower boundary areas of the damaged area and the normal area, 2–4 injection points10,000 single cells /μL500,000 cells / 50μL4.5# syringe needle (approved by the Food and Drug Admini stration)1 hPostoperative rehabilitation training3.47 ± 1.12 yrNoneThe average ASIA motor score of 108 cases increased from 37.79±18.45 to 41.25±18.18, the light touch score was from 50.32±24.71 to 55.90± 24.46, the pinprick score was from 50.53± 24.92 to 54.53±24.62; the IANR-SCIFRS score increased from 19.32±9.98 to 23.12±10.30. Suffi cient rehabilitation training has a signi ficant impact on the improvement of motor scores. 14 cases (12.96%) improved ASIA A to ASIA B; 18 cases (16.67%) improved ASIA A to ASIA C, 9 of which (8.33%) improved walking ability or they used walking device with or without help Walking; 12 of 14. males (14.29%) improved sexual function. Ele ctromyography was performed on 31 patients; 29 patients showed improve ment and the other 2 did not change signi ficantly. PVSEP test: of the 31 patients, 28 showed impro vement and the remaining 3 did not change.
Table 2Comparison of surgical parameters and clinical efficacy of spinal cord parenchyma transplantation using olfactory ensheathing cells.
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