scholarly journals Cell Therapies for Spinal Cord Injury: Trends and Challenges of Current Clinical Trials

Neurosurgery ◽  
2020 ◽  
Vol 87 (4) ◽  
pp. E456-E472
Author(s):  
Richard D Bartlett ◽  
Sarah Burley ◽  
Mina Ip ◽  
James B Phillips ◽  
David Choi
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
Cell Therapy ◽  
Early Phase ◽  
Basic Research ◽  
Great Promise ◽  
Cell Therapies ◽  
Human Spinal Cord ◽  
Cord Injury

Abstract Cell therapies have the potential to revolutionize the treatment of spinal cord injury. Basic research has progressed significantly in recent years, with a plethora of cell types now reaching early-phase human clinical trials, offering new strategies to repair the spinal cord. However, despite initial enthusiasm for preclinical and early-phase clinical trials, there has been a notable hiatus in the translation of cell therapies to routine clinical practice. Here, we review cell therapies that have reached clinical trials for spinal cord injury, providing a snapshot of all registered human trials and a summary of all published studies. Of registered trials, the majority have used autologous cells and approximately a third have been government funded, a third industry sponsored, and a third funded by university or healthcare systems. A total of 37 cell therapy trials have been published, primarily using stem cells, although a smaller number have used Schwann cells or olfactory ensheathing cells. Significant challenges remain for cell therapy trials in this area, including achieving stringent regulatory standards, ensuring appropriately powered efficacy trials, and establishing sustainable long-term funding. However, cell therapies hold great promise for human spinal cord repair and future trials must continue to capitalize on the exciting developments emerging from preclinical studies.

scholarly journals Pluripotent Stem Cells for Spinal Cord Injury Repair

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3334
Author(s):  
Maria Martin-Lopez ◽  
Beatriz Fernandez-Muñoz ◽  
Sebastian Canovas
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Cell Therapy ◽  
Pluripotent Stem Cells ◽  
Therapeutic Potential ◽  
Cell Types ◽  
Differentiation Potential ◽  
Cell Therapies ◽  
Cord Injury

Spinal cord injury (SCI) is a devastating condition of the central nervous system that strongly reduces the patient’s quality of life and has large financial costs for the healthcare system. Cell therapy has shown considerable therapeutic potential for SCI treatment in different animal models. Although many different cell types have been investigated with the goal of promoting repair and recovery from injury, stem cells appear to be the most promising. Here, we review the experimental approaches that have been carried out with pluripotent stem cells, a cell type that, due to its inherent plasticity, self-renewal, and differentiation potential, represents an attractive source for the development of new cell therapies for SCI. We will focus on several key observations that illustrate the potential of cell therapy for SCI, and we will attempt to draw some conclusions from the studies performed to date.

Extracorporeal shockwave therapy in spinal cord injury, early to advance to clinical trials? A systematic review and meta-analysis on animal studies

2021 ◽  
pp. 197140092110268
Author(s):  
Seyedeh Niloufar Rafiei Alavi ◽  
Arian Madani Neishaboori ◽  
Mahmoud Yousefifard
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
Animal Models ◽  
Meta Analysis ◽  
Mean Difference ◽  
Extracorporeal Shockwave Therapy ◽  
Extracorporeal Shockwave ◽  
Shockwave Therapy ◽  
Cord Injury

Background As there is no consensus over the efficacy of extracorporeal shockwave therapy in the management of spinal cord injury complications, the current meta-analysis aims to investigate preclinical evidence on the matter. Methods The search strategy was developed based on keywords related to ‘spinal cord injury’ and ‘extracorporeal shockwave therapy’. A primary search was conducted in Medline, Embase, Scopus and Web of Science until the end of 2020. Studies which administered extracorporeal shockwave therapy on spinal cord injury animal models and evaluated motor function and/or histological findings were included. The standardised mean difference with a 95% confidence interval (CI) were calculated. Results Seven articles were included. Locomotion was significantly improved in the extracorporeal shockwave therapy treated group (standardised mean difference 1.68, 95% CI 1.05–2.31, P=0.032). It seems that the efficacy of extracorporeal shockwave therapy with an energy flux density of 0.1 mJ/mm2 is higher than 0.04 mJ/mm2 ( P=0.044). Shockwave therapy was found to increase axonal sprouting (standardised mean difference 1.31, 95% CI 0.65, 1.96), vascular endothelial growth factor tissue levels (standardised mean difference 1.36, 95% CI 0.54, 2.18) and cell survival (standardised mean difference 2.49, 95% CI 0.93, 4.04). It also significantly prevents axonal degeneration (standardised mean difference 2.25, 95% CI 1.47, 3.02). Conclusion Extracorporeal shockwave therapy significantly improves locomotor recovery in spinal cord injury animal models through neural tissue regeneration. Nonetheless, in spite of the promising results and clinical application of extracorporeal shockwave therapy in various conditions, current evidence implies that designing clinical trials on extracorporeal shockwave therapy in the management of spinal cord injury may not be soon. Hence, further preclinical studies with the effort to reach the safest and the most efficient treatment protocol are needed.

scholarly journals AAV2-mediated and hypoxia response element-directed expression of bFGF in neural stem cells showed therapeutic effects on spinal cord injury in rats

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Sipin Zhu ◽  
Yibo Ying ◽  
Jiahui Ye ◽  
Min Chen ◽  
Qiuji Wu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
Control Group ◽  
Therapeutic Effects ◽  
Hypoxia Response Element ◽  
Neurofilament Protein ◽  
Response Element ◽  
Hypoxia Response ◽  
Cord Injury

AbstractNeural stem cell (NSCs) transplantation has been one of the hot topics in the repair of spinal cord injury (SCI). Fibroblast growth factor (FGF) is considered a promising nerve injury therapy after SCI. However, owing to a hostile hypoxia condition in SCI, there remains a challenging issue in implementing these tactics to repair SCI. In this report, we used adeno-associated virus 2 (AAV2), a prototype AAV used in clinical trials for human neuron disorders, basic FGF (bFGF) gene under the regulation of hypoxia response element (HRE) was constructed and transduced into NSCs to yield AAV2-5HRE-bFGF-NSCs. Our results showed that its treatment yielded temporally increased expression of bFGF in SCI, and improved scores of functional recovery after SCI compared to vehicle control (AAV2-5HRE-NSCs) based on the analyses of the inclined plane test, Basso–Beattie–Bresnahan (BBB) scale and footprint analysis. Mechanistic studies showed that AAV2-5HRE-bFGF-NSCs treatment increased the expression of neuron-specific neuronal nuclei protein (NeuN), neuromodulin GAP43, and neurofilament protein NF200 while decreased the expression of glial fibrillary acidic protein (GFAP) as compared to the control group. Further, the expressions of autophagy-associated proteins LC3-II and Beclin 1 were decreased, whereas the expression of P62 protein was increased in AAV2-5HRE-bFGF-NSCs treatment group. Taken together, our data indicate that AAV2-5HRE-bFGF-NSCs treatment improved the recovery of SCI rats, which is accompanied by evidence of nerve regeneration, and inhibition of SCI-induced glial scar formation and cell autophagy. Thus, this study represents a step forward towards the potential use of AAV2-5HRE-bFGF-NSCs for future clinical trials of SCI repair.

scholarly journals Impaired Organization of Paired-Pulse TMS-Induced I-Waves After Human Spinal Cord Injury

2015 ◽  
Vol 26 (5) ◽  
pp. 2167-2177 ◽  
Author(s):  
John Cirillo ◽  
Finnegan J. Calabro ◽  
Monica A. Perez
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Paired Pulse ◽  
Human Spinal Cord ◽  
Cord Injury

Feasibility of a Temporary Urethral Stent through the Striated Sphincter in Patients in the Early Phase (6 Months) of Spinal Cord Injury

2001 ◽  
Vol 39 (3) ◽  
pp. 326-331 ◽  
Author(s):  
Emmanuel J. Chartier-Kastler ◽  
Laurent Thomas ◽  
Bernard Bussel ◽  
Michael B. Chancellor ◽  
François Richard ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Early Phase ◽  
Cord Injury ◽  
Urethral Stent

The effects of methylprednisolone and the ganglioside GM1 on acute spinal cord injury in rats

1994 ◽  
Vol 80 (1) ◽  
pp. 97-111 ◽  
Author(s):  
Shlomo Constantini ◽  
Wise Young
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Body Weight Loss ◽  
Ganglioside Gm1 ◽  
Rat Spinal Cord ◽  
Neuroprotective Effects ◽  
Content Type ◽  
Human Spinal Cord ◽  
Cord Injury ◽  
Fine Print

✓ Recent clinical trials have reported that methylprednisolone sodium succinate (MP) or the monosialic ganglioside GM1 improves neurological recovery in human spinal cord injury. Because GM1 may have additive or synergistic effects when used with MP, the authors compared MP, GM1, and MP+GM1 treatments in a graded rat spinal cord contusion model. Spinal cord injury was caused by dropping a rod weighing 10 gm from a height of 1.25, 2.5, or 5.0 cm onto the rat spinal cord at T-10, which had been exposed via laminectomy. The lesion volumes were quantified from spinal cord Na and K shifts at 24 hours after injury and the results were verified histologically in separate experiments. A single dose of MP (30 mg/kg), given 5 minutes after injury, reduced 24-hour spinal cord lesion volumes by 56% (p = 0.0052), 28% (p = 0.0065), and 13% (p > 0.05) in the three injury-severity groups, respectively, compared to similarly injured control groups treated with vehicle only. Methylprednisolone also prevented injury-induced hyponatremia and increased body weight loss in the spine-injured rats. When used alone, GM1 (10 to 30 mg/kg) had little or no effect on any measured variable compared to vehicle controls; when given concomitantly with MP, GM1 blocked the neuroprotective effects of MP. At a dose of 3 mg/kg, GM1 partially prevented MP-induced reductions in lesion volumes, while 10 to 30 mg/kg of GM1 completely blocked these effects of MP. The effects of MP on injury-induced hyponatremia and body weight loss were also blocked by GM1. Thus, GM1 antagonized both central and peripheral effects of MP in spine-injured rats. Until this interaction is clarified, the authors recommend that MP and GM1 not be used concomitantly to treat acute human spinal cord injury. Because GM1 modulates protein kinase activity, protein kinases inhibit lipocortins, and lipocortins mediate anti-inflammatory effects of glucocorticoids, it is proposed that the neuroprotective effects of MP are partially due to anti-inflammatory effects and that GM1 antagonizes the effects of MP by inhibiting lipocortin. Possible beneficial effects of GM1 reported in central nervous system injury may be related to the effects on neural recovery rather than acute injury processes.

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