Asian Journal of Transfusion Science
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ORIGINAL ARTICLE Table of Contents   
Year : 2019  |  Volume : 13  |  Issue : 2  |  Page : 120-128
Effectiveness of bone marrow-derived mononuclear stem cells for neurological recovery in participants with spinal cord injury: A randomized controlled trial


1 Department of Orthopedic Surgery, King George's Medical University, Lucknow, Uttar Pradesh, India
2 Department of Transfusion Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India

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Date of Submission03-Apr-2018
Date of Acceptance02-Dec-2018
Date of Web Publication3-Dec-2019
 

   Abstract 


BACKGROUND: Complete lesion after spinal cord injury (SCI) remains irreversible with little hope of neurological recovery. Newer interventions such as re-stimulation of damaged neurons using artificial agents and the use of stem cells for neuronal regeneration have shown promising results.
AIM: This study was undertaken for evaluating the neurological status of acute SCI participants after stem cell augmentation and comparing them with other treatment methods.
SETTING AND DESIGN: Randomized controlled trial in the northern Indian population.
MATERIALS AND METHODS: A total 193 SCI participants of complete paraplegia with unstable T4–L2 injury having thoracolumbar injury severity score ≥4 were enrolled in this study. Participants were randomly allocated for three different treatment modalities, namely, conventional with stem cell augmentation (Group-1), conventional (Group-2), and conservative (Group-3). Neurological recovery after 1 year was evaluated through the ASIA Impairment Scale (AIS)-grading, sensory, and motor scores.
STATISTICAL ANALYSIS: T-test for sensory-motor score analysis of each group and analysis of variance for comparison of same variables between the groups.
RESULTS: After 1-year significant difference was observed in the AIS-grade, sensory and motor scores in-Group 1 (P < 0.001). In Group-1 versus 2, the mean difference at 1 year for AIS grade, sensory and motor scores were 0.40 (P = 0.010, 95% confidence interval [CI] 0.075–0.727), 8.52 (P = 0.030, 95% CI 0.619–16.419), and 4.55(P = 0.003, 95% CI 1.282–7.815), respectively. In Group-1 versus 3, 1.03, 19.02 and 7.22 (P < 0.001 for each of the parameters) and in Group-2 versus 3, 0.63 (P < 0.001), 10.49 (P = 0.009), and 2.68 (P = 0.019), respectively.
CONCLUSIONS: Significant motor neurological recovery and AIS-grade promotion was observed in Group-1 as compared to Group-2 and 3.

Keywords: Acute spinal cord injury, autologous bone marrow mononuclear stem cells, conventional treatment, neurological recovery, thoracolumbar injury severity score

How to cite this article:
Srivastava RN, Agrahari AK, Singh A, Chandra T, Raj S. Effectiveness of bone marrow-derived mononuclear stem cells for neurological recovery in participants with spinal cord injury: A randomized controlled trial. Asian J Transfus Sci 2019;13:120-8

How to cite this URL:
Srivastava RN, Agrahari AK, Singh A, Chandra T, Raj S. Effectiveness of bone marrow-derived mononuclear stem cells for neurological recovery in participants with spinal cord injury: A randomized controlled trial. Asian J Transfus Sci [serial online] 2019 [cited 2019 Dec 13];13:120-8. Available from: http://www.ajts.org/text.asp?2019/13/2/120/272056





   Introduction Top


Traumatic spinal cord injury (SCI) is a seriously debilitating disease with high mortality, and among survivors, a high degree of morbidity due to both motor and sensory deficit. Unfortunately, in spite of best efforts, little success has been achieved by any therapeutic modality in terms of neurological recovery.[1] The available modalities for neurological recovery produce only minor improvements.

Despite a great deal of advancement in therapeutics, the life expectancy, prognosis, functionality, and quality of life remain poor in SCI patients with impaired neurological status. The recovery rate in SCI patients remains poor with any type of treatment because the neuronal cells, which are already in the highly differentiated stage, have negligible regenerative power. Several researchers have attempted the induction of controlled differentiation of the fully-modified brain cells to turn back as undifferentiated progenitors, either by using a differentiation-inducing agent[2] or by stem cells application (trans-differentiation).[3] We have already conducted a study in support of this for neurogenesis enhancement and axonal re-myelination using olfactory ensheathing cells under defined media.[4] Further, our group had worked on ways to stimulate stem cells to regenerate neurons for functional recovery with promising results.

In SCI, the clinical application of embryonic, umbilical cord, adipose tissue, and bone marrow-derived mono-nuclear stem cells (BM-MNSCs) has been studied.[5] The advantages of using BM-MNSCs are: first, one can minimize all problems associated with the immunological rejection which are frequently caused in allogenic cell transplantation,[6] second, autologous cell infusion is considered safe by not being associated with carcinogenesis.[7]

Earlier, we conducted a Phase I trial to determine the safety and efficacy of noncultured autologous BM-MNSCs in the management of acute SCI (ASCI), and their role in neurological recovery.[8] There was a significant difference in percent mean recovery with stem cell application at the 12th month of follow-up.

The current study was performed to evaluate the effect of BM-MNSCs as an adjuvant to conventional management of traumatic SCI for neurological recovery.


   Materials and Methods Top


The current study, as Phase 2 trial, was conducted in the SCI Unit, Department of Orthopedic Surgery in collaboration with the Department of Transfusion Medicine, King George's Medical University (KGMU), Lucknow (UP), India from February 2013 to June 2016. This study was designed using the results of the Phase 1 randomized clinical trial on 110 ASCI participants to evaluate the safety and feasibility of application of BM-MNSCs and the role of surgery, omentoplasty and BM-MNSCs on clinical outcomes. Before this, the algorithm of aspiration, collection, isolation, and infusion of BM-MNSCs in SCI were standardized by us.[9]

Study population

The target population participating in this study was from Northern India and Nepal.

Study design

This is an open-label, individually randomized controlled, Phase II trial based on computer-generated random table (randomized controlled trial). As per random table, participants were randomized into three parallel groups [Supplementary Table 1 [Additional file 1]].
Table 1: General characteristics of subjects

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Study groups

  • Group 1 (Stem cell augmentation): ASCI participants managed by posterior instrumentation (titanium pedicle screw and rod devices) followed by infusion of autologous BM-derived stem cells as an adjuvant
  • Group 2 (Conventional): ASCI participants managed by posterior instrumentation (titanium pedicle screw and rod devices)
  • Group 3 (Conservative): ASCI participants managed nonoperatively.


Sample size calculation

The sample size was calculated by using mean difference and standard deviation (SD) of recovery based on ASIA scores of Group 1 and Group 3 participants from Phase 1 trial. The mean difference and SD of stem cell augmentation group versus conservative group were 8.118 and 14.9, respectively. The level of significance was set at 5% (Zα/2 =1.96) and the power of the study was 80% (Zβ= 0.84). On adding 10% loss in follow-up, each group had 60 participants with a total of 180 participants for all the three groups.

Selection criteria of the participants

Inclusion criteria

  • Participants of ASCI having complete lesion (ASIA Impairment Scale [AIS]-A grade) with thoracolumbar injury severity score (≥4) (unstable injury requiring stabilization by surgery)
  • Thoracolumbar spine injury level between T4 and L2 vertebra
  • Age between 18 and 65 years of either gender
  • Duration of injury <6 weeks
  • Sagittal continuity of the spinal cord and the presence of cord hemorrhage on MRI.


In MRI assessment of SCI, the axial and sagittal T2W images, and T2*W GRE images are particularly useful. The most common injuries following cord trauma are edema, hemorrhage, and a mixture of both.[10] Cord transaction patterns having worst prognosis are best predicted by the sagittal discontinuity of the spinal cord, whereas sagittal continuity provides a possibility of spinal cord containment within its sheath.[11],[12]

Exclusion criteria

  • Polytrauma patients with injury spine and associated thoraco-abdominal injuries and/or head injury
  • Medically unfit patients not suitable for surgery
  • Patients with other comorbid conditions such as osteoporosis, pressure sores (Grade III–IV), psychiatric illness and those on steroids or other immune suppressants
  • Patients who did not give their consent for participating in the study.


All enrolled participants were provided the standard surgical, medical as well as rehabilitation facilities. The assessment tool for recording the neurological status was the one proposed by the American Spinal Injury Association (ASIA). AIS grade, sensory, and motor scores were recorded at fixed time points after injury for neurological recovery. AIS Grade A, B, C, and D being nonparametric data were given numeric values such as 0, 1, 2, and 3, respectively, and then analyzed. In this study, we have documented neurological assessment at baseline and neurological recovery after 1 year [Supplementary Table 2 [Additional file 2]].
Table 2: Duration between injury to hospitalization and injury to management

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Intervention

Participants in all the groups were managed for pressure offloading by turning and repositioning them every 2 h. The normal curvatures of the spine were maintained with the help of pillows, and care of bladder and bowel was ensured in participants suffering from incontinence. Routine investigations of fitness for surgery and anesthesia were done for surgical Groups 1 and 2. Standard operating procedures were used for instrumentation of pedicle screw and rods under fluoroscopic control. Distraction or compression was applied if required for reduction and stabilization of the fracture. Adequacy of the reduction was confirmed in anterior-posterior and lateral fluoroscopic views.

In addition, for Group 1 participants, aspiration, isolation, and purification of autologous BM-MNSCs were done as per algorithm described in our earlier study.[9] BM aspiration was done for the preparation of stem cell concentrate required for autologous infusion. Approximately, 80–90 ml of autologous BM was aspirated from the posterior iliac crest and collected in primary CPDA bag of Quadruple CPDA-1 blood bag set. The crude BM was differentially centrifuged at 1200 rpm for 10 min at 10°C. The supernatant (plasma with nucleated cells) was transferred in one of the empty satellite bags of the quadruple set by using plasma expresser, making it rich in mononuclear cells along with leukocyte. It was then centrifuged at 2500 rpm for 10 min at 10°C and separated into a second empty satellite bag, leaving a precipitate (about 15 ml) of MNSCs in the first bag as a buffy coat. Approximately, 10 ml of precipitate was used for infusion and rest of the sample was sent for MNCs and CD34+ count which was found to have a mean count of 2.41 ± 1.198 × 106 live cells.

After fixation of the spine, spinous process of the fractured vertebra was removed along with portion of the lamina to visualize ligamentum flavum, which was excised for exposing the spinal cord. The dura mater of the spinal cord was held carefully with plain forceps at two different points separated by 1 cm distance. A stab incision with a #15 blade on a #7 knife handle was made in the dura mater up to the depth of arachnoid matter. Epidural catheter was placed in the subarachnoid space at the site of the injured cord. The arachnoid was closed over the catheter with silk 3–0. Fascia and skin closure was done leaving the other end of the tip of the catheter outside the stitched wound. The catheter was connected to the infusion pump, through which autologous stem cells were infused at the rate of 1 ml/h. The infiltration of infusion sample was done under aseptic condition in the postoperative room. After complete infusion of the BM-MNSCs, the catheter was pulled out carefully ensuring the presence of the blue tip at the end of the catheter, which confirms complete removal of the catheter from the spinal cord.

After 48 h of surgery, in both the surgery groups, the SCI participants were mobilized on a wheelchair with anterior hyper-extension braces. Following removal of stitches, preferably on the 10th day, the participants were transferred to the Department of Physical Medicine and Rehabilitation for structured rehabilitation protocol. The SCI participants of Group 3 were provided the same rehabilitation facilities as provided to both surgical groups. The facilities included early mobilization depending on neurological status, physiotherapy to facilitate recovery and prevention of known complications along with vocational training. The most common complications seen following ASCI were pressure sores, contractures, spasticity, bladder, bowel, and sexual dysfunction. SCI participants were followed-up in ortho outpatient department at 3-month interval for 1 year.

Statistical analysis

Data of all the participants were collected at the time of admission (baseline) and after 1 year (as follow-up). Data were analyzed using statistical analysis software packages, namely, Statistical Package for Social Sciences (SPSS) version 16 (South Wacker Drive, Chicago, IL, USA). 0 and GraphPad. Paired t-test was used to compare AIS grades, motor, and sensory scores at baseline and follow-up in terms of mean and (mean ± SD) with 95% confidence interval (CI) at 5% level of significance. Groups were compared with each other using one-way analysis of variance with Bonferroni Correction Post hoc analysis to evaluate the mean difference, 95% CI and related P values of AIS grade, sensory, and motor scores after 1 year.

Desirable outcomes

BM-MNSCs augmentation improves neurological recovery in ASCI.

Statement of ethics

This study was approved by the Ethics Committee (IEC 60th ECM II-B/P14) and stem cell ethics committee (02/ISCES-12) of KGMU. The trial is registered under the Clinical Trial Registry of India (acknowledgment no. is REF/2017/08/015121). The study procedure was explained to all the participants in their native language. Written informed consent was also obtained from all the participants.


   Results Top


Participants were recruited as per inclusion criteria and divided into three groups according to the treatment plan. A total of 220 participants were enrolled for the study. Twenty-seven out of 220 participants could not complete the study either due to drop out in between the study or lost to follow-up. Finally, 193 participants who could be followed for a year were included. Group 1 had 70 participants who underwent conventional surgery along with BM-MNSCs as an adjuvant. In Group 2, there were 68 participants who were treated by conventional surgery and Group 3 included 55 participants who underwent nonoperative conservative therapy. The maximum drop out was seen in the conservative group because of the nonoperative treatment mode, in which participants were not willing for follow-up. As pretreatment record, the complete neurological assessment was done at baseline using AIS grading, sensory, and motor scores. After 1 year, the neurological assessment was again performed and compared with baseline values.

Demographic information

Majority of the participants were men, 166 individuals (86.01%) and 28 were female (13.99%). All the groups had male dominance (Groups 1, 2, and 3 had 90%, 85.29%, and 80% of male participants, respectively) [Table 1]. The age group of 18–30 years was most prone to SCI followed by other age groups. The mean age of Groups 1, 2, and 3 were 30.84 ± 10.56, 31.30 ± 9.74, and 33.42 ± 12.07 years, respectively [Table 2]. Fall from height (70.98%) and road traffic accident (16.58%) were the two most common modes of injury in our study. The group-wise distribution of age and mode of injury were almost the same in all the three groups [Table 1]. The mean ± SD of admission within 2 weeks for Groups 1, 2, and 3 were 3.61 ± 2.84, 4.7 ± 4.12, and 5.14 ± 3.84 with CI of 2.78–4.45, 3.26–6.14, and 3.62–6.66, respectively. Almost the similar trend was seen in groups whose participants were admitted between 2–4 and 5–6 weeks. The mean ± SD of management within 2 weeks of injury for Groups 1 and 2 were 6.07 ± 1.90 and 6.75 ± 2.63, respectively. Again, a similar trend was seen in participants of both the groups who were managed between 2–4 and 5–6 weeks of injury [Table 2].

ASIA Impairment Scale grade comparison

After 1 year of follow-up, improvements in sensory and motor abilities were observed in participants of all the groups, wherein the stem cell group showed the best results. In AIS grading, significant improvement was observed in Group 1 as compared to that of other groups. In Group 1, 21.43% of participants remained in AIS A, whereas the percentage improvement to AIS B, C, and D was 30%, 41.43%, and 7.14%, respectively, whereas in Group 2, the AIS A, B, C, and D values were 32.82%, 38.24%, 27.94%, and 0.0% and in Group 3, these were 78.18%, 12.73%, 9.09%, and 0.0%, respectively [Table 3].
Table 3: American Spinal Injury Association impairment scale grades in different groups at baseline and 1 year

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Baseline mean values for AIS grade, sensory and motor scores were 0 ± 0, 144.03 ± 14.91, and 50 ± 0, respectively, in Group 1. After 1 year, the mean values increased to 1.34 ± 0.9 (95% CI: 1.56–1.13), 169.34 ± 18.62 (95% CI: 30.08-20.55), and 58.83 ± 10.70 (95% CI: −11.38–−6.28), respectively, with P < 0.001 for each of the above parameters. In “Group 2,” baseline mean values for the above three parameters were 0 ± 0, 147.24 ± 16.56, 50 ± 0, and after 1 year were increased to 0.94 ± 0.79 (95% CI: 1.13–0.75), 160.82 ± 21.44 (95% CI:-16.44 to-10.73), and 54.28 ± 6.31 (95% CI:-5.81 to-2.75), respectively, with P < 0.001 for each parameter. These data indicate that in all the three parameters, the AIS grades, sensory, and motor scores highly significant improvement was observed in both the surgery groups (stem cell augmentation group and conventional group). In “Group 3” (conservative, nonoperative group) baseline mean values were 0 ± 0, 148.33 ± 15.37, 50 ± 0, respectively, whereas, after 1 year values increased to 0.31 ± 0.63 (P = 0.0007, % CI: 0.48–0.14), 150.33 ± 16.87 (P = 0.19, % CI: 5.03–1.03), 51.60 ± 5.13 (P = 0.0245, 95% CI: −2.99–−0.21), respectively, and were highly significant in AIS grading only [Table 4].
Table 4: Intra-group comparison of American Spinal Injury Association impairment scale grades, sensory, and motor scores at baseline and 1 year

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A Post_hoc analysis was performed for inter-group analysis to compare AIS grades, sensory, and motor scores in all the three groups (Group 1 vs. 2, 1 vs. 3, and 2 vs. 3) at baseline and after 1 year. The mean difference values for the AIS grade assessment were 0.40 (P = 0.010, 95% CI 0.075–0.727), 1.03 (P< 0.001, 95% CI 0.688–1.378), and 0.63 (P< 0.001, 95% CI 0.285–0.979) in Group 1 versus 2, 1 versus 3, and 2 versus 3, respectively. The mean difference values of sensory scores for treatment Group 1 versus 2, 1 versus 3, and 2 versus 3 were 8.52 (P = 0.030, 95% CI 0.619–16.419), 19.02 (P< 0.001, 95% CI 10.285–27.375), and 10.49 (P = 0.009, 95% CI 2.082–18.910), respectively. Similarly, the mean difference values of motor scores were 4.55(P = 0.003, 95% CI 1.282–7.815), 7.22 (P< 0.001, 95% CI −3.77–10.685), and 2.68 (P = 0.019, 95% CI −0.799–6.158), respectively [Table 5]. These results indicate Group 1 (stem cell augmentation) had statistically significant difference from Group 2 and 3 in all the three specified parameters.
Table 5: Inter-group analysis of the American Spinal Injury Association impairment scale grading, sensory, and motor scores after 1 year

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   Discussion Top


Traumatic injury to the spinal cord immediately causes primary insult to the neural tissue, which remains irreversible and resistant to any intervention.[13],[14],[15] After the primary injury, the inflammatory process gets activated and leads to secondary injury phase.[16] The main hindrance in the process of neuronal regeneration is growth inhibitors present at the site of injury.[17] Earlier studies were mostly focused on preventing and reducing the extent of secondary injury which may further damage the spinal cord.[18],[19] An initial surgery is usually performed to provide support to damaged tissues and reduce the compression impact.[20],[21] Surgery helps in spinal stabilization, preventing spinal deformity, and facilitating patient mobility but not in neurological recovery.[22]

The available modalities for neurological recovery include the use of steroids and GM-1 ganglioside,[19] functional electrical stimulation,[23] retraining neural circuits to restore body functions, use of adaptive devices for communication, physical and occupational therapy, rehabilitation, and self-grooming techniques.[24]

The repair of already damaged neurons may be initiated by stimulation of factors responsible for neuronal repair and regeneration. Studies have shown that stem cells can be stimulated to form new neurons, but their contribution to the healing process has not been supported by sufficient evidence.[25] It has been observed by the studies that intrinsic adult stem cells and progenitor cells accumulate at the site of cord injury and help in neural tissue repair.[26] Neural progenitor cells secrete neurotropic factors, triggering the growth of injured neurons.[27] Stem cells make axons incapable of recognizing growth inhibitory molecules leading to axonal growth.[13] Activities such as walking and sensory perception have shown marked improvement over time with stem cell therapy.[14] Hematopoietic stem cells indirectly improve muscle strength and nerve regeneration,[28],[29] whereas other studies suggested the use of granulocyte macrophage colony stimulating factor for the same.[30]

This study was performed to evaluate the effect of BM-MNSCs, used as an adjuvant, to conventional management[31] of traumatic SCI for neurological recovery. The results show that neurological recovery is better with stem cell augmentation in SCI surgery. According to the WHO, the global incidence of SCI is between 40 and 80 per million of population per year.[32] The increasing incidences and persisting poor prognosis in neurological recovery cause despair in SCI participants and helplessness among physicians involved in their management.[33] Unfortunately, no progress has been possible to reverse the primary injury caused to the spinal cord. Earlier studies were mostly focused on preventing and reducing the extent of the secondary injury and empowering people with SCI to return to an active and productive life. Researchers have been continually working on new treatments, including prostheses and medications that may promote nerve cell regeneration or improve the function of the nerves after ASCI.[34]

In this study, the mean age of the participants was 31.74 years. The results indicate that youngsters are more prone to SCI. It may be because they are more active, courageous, and live an aggressive lifestyle. In contrast to participants from Western countries, the most common types of injuries in our study were fall from height (70.98%) followed by road traffic accidents (16.58%). This may be because in developing countries in rural areas, from where most of these participants arrive, fall from trees and uncovered roofs are common.[35] This study was restricted to traumatic paraplegia participants only. Traumatic paraplegia is the result of damage to the cord at T2 level and below. To overcome the possibility of ascending edema following ASCI, in our study, participants of traumatic paraplegia having a complete lesion with the level of injury between T4 and L2 were included, to avoid any chance of SCI participants having quadriplegia. The most common vertebral level involved in our participants was between T10 and L2. Several studies have correlated “fall from height” with the injury of thoracolumbar junction (T10–L2).[36]

Many studies have reported no significant improvement in SCI, if surgery is delayed by more than 3 weeks.[37] In this study, the majority of participants were operated within 2 weeks of admission, but due to the late arrival of some participants, the duration between the injury to surgery reached up to 6 weeks. The participants reach late because in developing countries; besides lack of awareness, illiteracy, and poverty, there are misconceptions and superstitions, which hinder early-specialized health care services.[38] Despite the late presentation of participants after injury, we have found significant improvement in the neurological recovery in all the groups. Participants operated within 2 weeks and those operated later had similar outcomes. Delay in surgery up to 6 weeks of injury did not affect recovery. In this study, we have used AIS grades to determine the severity of ASCI in participants. In comparison to the baseline information, there is an improvement in follow-up after 1 year. Group 1 shows maximum recovery, wherein 30% AIS Grade A achieved AIS Grade B, 41.43% Grade C, and 7.14% Grade D, which is quite remarkable. Group 2 shows recovery with 38.24% in AIS Grade B and 27.94% in Grade C. The reason for better recovery in Group 1 as compared to that of Group 2 could probably be attributed to stem cell augmentation, as this was the only factor that was different in the two groups. Group 3 also shows some recovery, but 78.18% of participants remained in the AIS grade A.

The recovery seen in the conservative group is due to spontaneous regeneration of neurons and is dependent on the physiology of participants. Various studies have shown that recovery in the conventional group is better than that in the conservative group because surgery provides stability to the spine and helps in the recovery of the injured spinal column. Surgery also reduces the possibility of further damage and arrests the secondary injury phase after ASCI.[39] Decompressing the spinal cord further relieves the pressure on the cord and improves its vascularity. The recovery of participants in the conventional group was better as compared to those of conservative group, but was low as compared to that of the stem cell augmentation group. The plausible explanation for this is that the BM-MNSCs can repair the damaged area and may induce recovery by signals provided by the activators and inhibitors present at a particular niche of the damaged area. After infusion, BM-MNSCs also get converted into various types of cells (neurons, astrocytes, and oligodendrocytes) as per the requirement of the damaged site. Application of stem cells as an adjuvant at the site of injury provided the favorable environment for neurological recovery by attracting biochemicals required for the accelerated initiation, cell division, and differentiation of progenitor cells of peripheral blood into required cell types. At the same time, infused stem cells differentiate into neurons under the influence of existing biochemical environment caused by trauma.[40]

AIS evaluation has been performed at two specific stages, first, at admission (pre-treatment) and the other after one year of follow-up. Mean values for AIS grade, sensory, and motor scores for Group 1 and Group 2 were 1.34, 169.34, 58.83 and 0.94, 160.82, and 54.28, respectively. A significant difference was found between both the groups with stem cell group showing better results in all the three parameters. Group 3 scores were almost similar to the baseline, which suggests a very small recovery. The results suggest that stem cells have a role in neurological recovery. Surgical methods are better than conservative treatment was also established by the scores and the AIS grades achieved after 1 year in all the groups.

Comparison among the groups was made to obtain mean difference values and P values of significance for AIS grade, sensory, and motor scores. The significant mean difference values of sensory scores were 8.52, 19.02, and 10.49, respectively, for all comparison groups (Group 1 vs. 2, 1 vs. 3, and 2 vs. 3). Group 1 had a statistically significant difference from Group 2 to 3 in all the three specified parameters. Group 2 also showed a statistically significant difference from Group 3 in some of parameters, but the result shown by participants of Group 1 versus 3 is not so robust.

Enumerating the strength of this study, it is based on our pilot study in which participants of ASCI were treated with stem cells. This study had standard outcome measures with clear documentation and data management to ensure reproducibility. A properly matched baseline characteristics in all the participants minimized confounders. The maximum participation of participants throughout the follow-up period was ensured by staying in touch with them and their attendants, either by phone or through home visits. Finally, participants participating in this study represented a large geographical area to minimize the regional variation bias, and to ensure that the results will be representative of the population studied. The limitations of this study were the exclusion of SCI cases having tetraplegia (cervical and cervicothoracic lesions), SCI >6-week-old, the inclusion of AIS A participants only (complete lesions) and the concern of spontaneous recovery seen in SCI which may lead to clinician's bias in interpretation of results. Then, although we have infused 2.41 ± 1.198 × 106 (mean count) of live stem cells, but did not correlate them individually with the recovery. It was because of ethical reasons that we could not take the BM from conventional and conservative group participants for stem cell count. Furthermore, at the end of follow-up, the number of participants in each group was unequal and the conservative group had the least number of participants. This group had a general thought that, as they were not operated, there was not much need of regular follow-up. Nonetheless, fortunately, the numbers of participants in both the surgery groups were more than the required sample size of 60 in each group and only five short (55) in the conservative group.


   Conclusions Top


This study concluded that the conventional treatment by surgery to stabilize the unstable spine gave better results over conservative treatment. The results of delayed surgery by up to 6 weeks were comparable with those of early surgery. The synergistic use of stem cells as an adjuvant with conventional treatment showed the best recovery results among all the specified groups and ultimately stresses on the significant role of BM-MNSCs in SCI. Application of stem cells as an adjuvant at the site of injury provided the favorable environment and the precursors for neurological recovery.

Acknowledgments

There was no external source of funding. Our institute is a state government organization and the required facilities for research are already available. All the procedure of research and intervention provided to participants were totally free of cost.

The authors acknowledge the contribution of the following personnel for their guidance and assistance during the initiation, conduction, and completion of this study-Prof. Saroj Chooramani Gopal, Department of Paediatric Surgery, IMS-BHU, Varanasi, India. Prof. G. K. Singh, Prof. Ajai Singh, Dr. Abhishek Agrawal, and Dr. Tribhav Goel, Department of Orthopaedic Surgery, KGMU, Lucknow, India. Prof. R. K. Garg, Department of Neurology, Prof. A. A. Mahdi, Department of Biochemistry, Dr. Chhitij Srivastava, Department of Neurosurgery, Prof. Abhijit Chandra, Department of Surgical Gastroenterology and Dr. Anit Parihar, Department of Radiology, KGMU, Lucknow, India. Prof. Raja Roy, Centre of Biomedical Research, SGPGIMS, Lucknow, India and Dr. Rajneesh K. Chaturvedi, Senior Scientist, Indian Institute of Toxicology Research, Lucknow, India.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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[PUBMED]  [Full text]  
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Correspondence Address:
Rajeshwar Nath Srivastava
Department of Orthopedic Surgery, King George's Medical University, Nabiullah Road, Daliganj, Lucknow - 226 018, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ajts.AJTS_44_18

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2006 - Asian Journal of Transfusion Science | Published by Wolters Kluwer - Medknow
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