Effectiveness of bone marrow-derived mononuclear stem cells for neurological recovery in participants with spinal cord injury: A randomized controlled trial

Srivastava, Rajeshwar Nath; Agrahari, Ashok Kumar; Singh, Alka; Chandra, Tulika; Raj, Saloni

doi:10.4103/ajts.ajts_44_18

Cited by 6 publications

(5 citation statements)

References 33 publications

(33 reference statements)

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“…It is worth noting that the ASIA score-based assessment of sensory and motor function relies on subjective evaluation by the assessor and the patient, reducing result reliability to a certain extent [ 88 ]. Although this observed rate of 48.9% is lower than the rate of 78.57% obtained by Srivastava et al in a randomized controlled trial with 200 patients [ 69 ] and the rate of 70% observed by Cheng et al [ 31 ], given that small functional improvements are also extremely important for patient survival and well-being, stem cell therapy for SCI remains promising. Meanwhile, an increasing number of patients believe that the recovery of intestinal and bladder functions is as or more important than walking.…”

Section: Discussioncontrasting

confidence: 58%

Clinical translation of stem cell therapy for spinal cord injury still premature: results from a single-arm meta-analysis based on 62 clinical trials

Shang

Wang

Zhang

et al. 2022

BMC Med

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Background How much scientific evidence is there to show that stem cell therapy is sufficient in preclinical and clinical studies of spinal cord injury before it is translated into clinical practice? This is a complicated problem. A single, small-sample clinical trial is difficult to answer, and accurate insights into this question can only be given by systematically evaluating all the existing evidence. Methods The PubMed, Ovid-Embase, Web of Science, and Cochrane databases were searched from inception to February 10, 2022. Two independent reviewers performed the literature search, identified and screened the studies, and performed a quality assessment and data extraction. Results In total, 62 studies involving 2439 patients were included in the analysis. Of these, 42 were single-arm studies, and 20 were controlled studies. The meta-analysis showed that stem cells improved the ASIA impairment scale score by at least one grade in 48.9% [40.8%, 56.9%] of patients with spinal cord injury. Moreover, the rate of improvement in urinary and gastrointestinal system function was 42.1% [27.6%, 57.2%] and 52.0% [23.6%, 79.8%], respectively. However, 28 types of adverse effects were observed to occur due to stem cells and transplantation procedures. Of these, neuropathic pain, abnormal feeling, muscle spasms, vomiting, and urinary tract infection were the most common, with an incidence of > 20%. While no serious adverse effects such as tumorigenesis were reported, this could be due to the insufficient follow-up period. Conclusions Overall, the results demonstrated that although the efficacy of stem cell therapy is encouraging, the subsequent adverse effects remain concerning. In addition, the clinical trials had problems such as small sample sizes, poor design, and lack of prospective registration, control, and blinding. Therefore, the current evidence is not sufficiently strong to support the clinical translation of stem cell therapy for spinal cord injury, and several problems remain. Additional well-designed animal experiments and high-quality clinical studies are warranted to address these issues.

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Section: Discussioncontrasting

confidence: 58%

Clinical translation of stem cell therapy for spinal cord injury still premature: results from a single-arm meta-analysis based on 62 clinical trials

Shang

Wang

Zhang

et al. 2022

BMC Med

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“…In the rat SCI model of severe contusion injury, no stem cell treatment has so far succeeded in repairing the tissue loss in the lesion center. Despite this, a benefit on functional recovery is observed justifying clinical trials [8,28].…”

Section: Discussionmentioning

confidence: 99%

“…However, in preparatory experiments we found that spinal cord injection per se caused additional damage. This application may be more effective for interventions in the chronic phase, when cells can be implanted into the cavity within the spinal cord that has formed by then [11,28].…”

Section: Steroid Treatment and Limitations Of The Present Studymentioning

confidence: 99%

Treatment of rats with spinal cord injury using human bone marrow-derived stromal cells prepared by negative selection

Romero‐Ramírez

Munter³

et al. 2020

J Biomed Sci

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Background: Spinal cord injury (SCI) is a highly debilitating pathology without curative treatment. One of the most promising disease modifying strategies consists in the implantation of stem cells to reduce inflammation and promote neural regeneration. In the present study we tested a new human bone marrow-derived stromal cell preparation (bmSC) as a therapy of SCI.Methods: Spinal cord contusion injury was induced in adult male rats at thoracic level T9/T10 using the Infinite Horizon impactor. One hour after lesion the animals were treated with a sub-occipital injection of human bmSC into the cisterna magna. No immune suppression was used. One dose of bmSC consisted, on average, of 2.3 million non-manipulated cells in 100 μL suspension, which was processed out of fresh human bone marrow from the iliac crest of healthy volunteers. Treatment efficacy was compared with intraperitoneal injections of methylprednisolone (MP) and saline. The recovery of motor functions was assessed during a surveillance period of nine weeks. Adverse events as well as general health, weight and urodynamic functions were monitored daily. After this time, the animals were perfused, and the spinal cord tissue was investigated histologically.Results: Rats treated with bmSC did not reject the human implants and showed no sign of sickness behavior or neuropathic pain. Compared to MP treatment, animals displayed better recovery of their SCI-induced motor deficits. There were no significant differences in the recovery of bladder control between groups. Histological analysis at ten weeks after SCI revealed no differences in tissue sparing and astrogliosis, however, bmSC treatment was accompanied with reduced axonal degeneration in the dorsal ascending fiber tracts, lower Iba1-immunoreactivity (IR) close to the lesion site and reduced apoptosis in the ventral grey matter. Neuroinflammation, as evidenced by CD68-IR, was significantly reduced in the MP-treated group.Conclusions: Human bmSC that were prepared by negative selection without expansion in culture have neuroprotective properties after SCI. Given the effect size on motor function, implantation in the acute phase was not sufficient to induce spinal cord repair. Due to their immune modulatory properties, allogeneic implants of bmSC can be used in combinatorial therapies of SCI.

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“…BM-MSCs promote axonal regeneration by guiding nerve fibers and hence eliminate glial scars in the injured spinal cord [27][28][29]. The precise mechanism by which transplantation of bone marrow-derived MSCs (BM-MSCs) promotes functional recovery after SCI is still unclear [30][31]. Cell transplantation is a targeted new promising therapeutic strategy for spinal cord regeneration based on a series of animal and clinical studies, and it has been previously reported that stem cells have a potential effect on the SCI treatment [32-33, 24, 35].…”

Section: Discussionmentioning

confidence: 99%

“…Song et al 2020[16] Albu, et al 2021[20] Yoon, et al 2007[23] El-Kheir, et al 2014[25] Kishk NA, et al 2010[27] Sharma A, et al 2020[29] Park, et al 2012[31] e218 Role of stem cells transplantation for patients with spinal cord injury: systematic meta-analysis J Popul Ther Clin Pharmacol Vol 30(7):e211-e221; 06 April 2023. This article is distributed under the terms of the Creative Commons Attribution-Non Commercial 4.0 International License.…”

mentioning

confidence: 99%

Role of stem cells transplantation for patients with spinal cord injury: systematic meta-analysis

2023

JPTCP

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Background: Spinal cord injury is a devastating condition that leads to physical, social, and vocational impairment due to the irreversible loss of neural function below the injury site. The objective of this study is to investigate the efficacy and safety of bone marrow mononuclear cells (BM-MNCs) transplant in patients with spinal cord Injury in systematic meta-analysis. Methods: This systematic review and meta-analysis study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The authors searched the PubMed, Web of Science, Cochrane, and Embase databases, OVID, China Biomedical Database (CBM), SinoMed databases and Library databases up to March 15, 2022. Inclusion criteria included for quantitative review, two well-trained author's retrieved independently relevant data from articles included for analysis and cross-checked it. In case of disagreements, a third party was consulted to reach a consensus. The methodological quality of the included studies was assessed independently by two reviewers using the Cochrane Collaboration's ROBINS-I tool for non-randomized studies. Results: Preliminary search database resulted in 549 articles, finally, after excluded all articles did not meet the study criteria 26 studies were included in study and 569 Spinal cord injury patients were included for qualitative analysis in this meta-analysis. Male 77.9% with male/female ration 485/84 variability in the age among included studies. Resulted data showed minor adverse events after bone marrow mononuclear cells (BM-MNCs) transplant; low heterogeneity was observed across each trial (P = 0.11, I2 = 38%). The average risk ratio of these studies was 10.12 (95%CI: 4.24-29.12, p < 0.00003) without heterogeneity (p = 0.81, I2 = 0%) between studies. The methodological quality of the included studies used the standard Cochrane Collaboration tool to analysis is the risk of bias. Conclusions: Bone marrow mononuclear cells (BM-MNCs) significantly improve neurological function in patients with spinal cord injury. Furthermore, this type of procedures has no systemic nor serious complications after autologous transplantation.

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Effectiveness of bone marrow-derived mononuclear stem cells for neurological recovery in participants with spinal cord injury: A randomized controlled trial

Cited by 6 publications

References 33 publications

Clinical translation of stem cell therapy for spinal cord injury still premature: results from a single-arm meta-analysis based on 62 clinical trials

Clinical translation of stem cell therapy for spinal cord injury still premature: results from a single-arm meta-analysis based on 62 clinical trials

Treatment of rats with spinal cord injury using human bone marrow-derived stromal cells prepared by negative selection

Role of stem cells transplantation for patients with spinal cord injury: systematic meta-analysis

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