Human Neural Stem Cell Transplantation in Chronic Cervical Spinal Cord Injury

Ghobrial, George M.; Anderson, Kim D.; Dididze, Marine; Martinez-Barrizonte, Jasmine; Sunn, Gabriel H.; Gant, Katie; Levi, Allan D.

doi:10.1093/neuros/nyx242

Cited by 53 publications

(31 citation statements)

References 34 publications

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“…Despite these limitations, clinical and preclinical studies evaluating effects of transplanting several different cell types, including NSPCs, MSCs, Schwann cells, OPCs, and OECs, have shown promising results to date. 1,6,17 NSPCs have been derived from human fetal spinal cord, 63,75 human fetal brain, 44,72,76 or pluripotent or ESCs 64 and can differentiate into the glial and neuronal cells, which normally make up the spinal cord. MSCs, including those derived from adipose tissue (A-MSCs), 77 umbilical cord blood, 78 and Wharton's jelly, 79 human OPCs derived from human ESC (hESC) lines, 64 and human NSPCs derived from fetal spinal cord tissues 63 have been investigated in clinical trials.…”

Section: Neuroregenerative and Neuroprotective Therapiesmentioning

confidence: 99%

Regenerative Therapies for Spinal Cord Injury

Ashammakhi

Kim

Ehsanipour

et al. 2019

Tissue Engineering Part B: Reviews

117

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Spinal cord injury (SCI) is a serious problem that primarily affects younger and middle-aged adults at its onset. To date, no effective regenerative treatment has been developed. Over the last decade, researchers have made significant advances in stem cell technology, biomaterials, nanotechnology, and immune engineering, which may be applied as regenerative therapies for the spinal cord. Although the results of clinical trials using specific cell-based therapies have proven safe, their efficacy has not yet been demonstrated. The pathophysiology of SCI is multifaceted, complex and yet to be fully understood. Thus, combinatorial therapies that simultaneously leverage multiple approaches will likely be required to achieve satisfactory outcomes. Although combinations of biomaterials with pharmacologic agents or cells have been explored, few studies have combined these modalities in a systematic way. For most strategies, clinical translation will be facilitated by the use of minimally invasive therapies, which are the focus of this review. In addition, this review discusses previously explored therapies designed to promote neuroregeneration and neuroprotection after SCI, while highlighting present challenges and future directions.

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Section: Neuroregenerative and Neuroprotective Therapiesmentioning

confidence: 99%

Regenerative Therapies for Spinal Cord Injury

Ashammakhi

Kim

Ehsanipour

et al. 2019

Tissue Engineering Part B: Reviews

117

View full text Add to dashboard Cite

show abstract

“…Based on these preliminary data, several early-phase clinical trials were performed. These demonstrated that transplantation of human fetal brain-or spinal cord-derived NSPCs is generally feasible and safe, and yields minimal or modest neurological improvement; however, the long-term efficacy and safety remain unproven [18][19][20]. The patterns of cellular responses to SCI are extremely heterogeneous and complex; therefore, simply delivering specific neural cell types into the injured spinal cord via cell or stem cell therapy is ineffective [44].…”

Section: Discussionmentioning

confidence: 99%

Glial Cell Line-derived Neurotrophic Factor-overexpressing Human Neural Stem/Progenitor Cells Enhance Therapeutic Efficiency in Rat with Traumatic Spinal Cord Injury

et al. 2019

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Spinal cord injury (SCI) is a devastating neurological disorder that leads to motor, sensory, or autonomic dysfunction, and is associated with high rates of mortality and complications including bladder infection, renal failure, cardiovascular disease, and respiratory dysfunctions. There are approximately 180,000 new cases of SCI worldwide per year caused by traffic accidents, sports injuries, and other traumatic events according to an epidemiologic study

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“…In a clinical trial that transplanted human NSPCs into subacute SCI patients, immunosuppression was performed from 3 days prior to transplantation until 9 weeks after transplantation 47) . In a recent clinical study in which human NSPCs were transplanted into chronic cervical SCI patients, all subjects received immunosuppression regimens prior to engraftment and these were continued until 6 months post-transplantation to prevent graft rejection and mitigate any potential post-transplantation inflammatory responses 15) .…”

Section: Comparison Of Mscs and Nspcsmentioning

confidence: 99%

Current Status and Future Strategies to Treat Spinal Cord Injury with Adult Stem Cells

Jeong

Choi

Jeon

2020

J Korean Neurosurg Soc

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Spinal cord injury (SCI) is one of the most devastating conditions and many SCI patients suffer neurological sequelae. Stem cell therapies are expected to be beneficial for many patients with central nervous system injuries, including SCI. Adult stem cells (ASCs) are not associated with the risks which embryonic stem cells have such as malignant transformation, or ethical problems, and can be obtained relatively easily. Consequently, many researchers are currently studying the effects of ASCs in clinical trials. The environment of transplanted cells applied in the injured spinal cord differs between the phases of SCI; therefore, many researchers have investigated these phases to determine the optimal time window for stem cell therapy in animals. In addition, the results of clinical trials should be evaluated according to the phase in which stem cells are transplanted. In general, the subacute phase is considered to be optimal for stem cell transplantation. Among various candidates of transplantable ASCs, mesenchymal stem cells (MSCs) are most widely studied due to their clinical safety. MSCs are also less immunogenic than neural stem/progenitor cells and consequently immunosuppressants are rarely required. Attempts have been made to enhance the effects of stem cells using scaffolds, trophic factors, cytokines, and other drugs in animal and/or human clinical studies. Over the past decade, several clinical trials have suggested that transplantation of MSCs into the injured spinal cord elicits therapeutic effects on SCI and is safe; however, the clinical effects are limited at present. Therefore, new therapeutic agents, such as genetically enhanced stem cells which effectively secrete neurotrophic factors or cytokines, must be developed based on the safety of pure MSCs. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Human Neural Stem Cell Transplantation in Chronic Cervical Spinal Cord Injury

Cited by 53 publications

References 34 publications

Regenerative Therapies for Spinal Cord Injury

Regenerative Therapies for Spinal Cord Injury

Glial Cell Line-derived Neurotrophic Factor-overexpressing Human Neural Stem/Progenitor Cells Enhance Therapeutic Efficiency in Rat with Traumatic Spinal Cord Injury

Current Status and Future Strategies to Treat Spinal Cord Injury with Adult Stem Cells

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