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Improving the therapeutic efficacy of neural progenitor cell transplantation following spinal cord injury.

ABSTRACT: There have been a wide range of preclinical studies testing cellular therapies to repair the injured spinal cord, yet they remain a challenge to translate because of inconsistencies in efficacy, limited number of patients with acute/subacute SCI and the high costs of clinical trials. Area covered: This paper focusses on the therapeutic potential of neural precursor cells (NPCs) because they can provide the cellular components capable of promoting repair and enhancing functional improvement following spinal cord injury (SCI). The authors discuss the challenges of NPC transplantation with respect to different populations of NPCs of glial and neuronal lineages, the timing of treatment relative to acute and chronic injury, and the progress in ongoing clinical trials. Expert commentary: Preclinical research will continue to elucidate mechanisms of recovery associated with NPC transplants, including increasing the partnership with related fields such as spinal atrophies and multiple sclerosis. The clinical trials landscape will grow and include both acute and chronic SCI with increased partnership and strengthened communication between biotechnology, government and academia. There will also be growing effort to develop better biomarkers, imaging and outcome measures for detailed assessment of neurological function and measures of quality of life.

SUBMITTER: Lane MA

PROVIDER: S-EPMC5368014 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Improving the therapeutic efficacy of neural progenitor cell transplantation following spinal cord injury.

Lane Michael A MA Lepore Angelo C AC Fischer Itzhak I

Expert review of neurotherapeutics 20161221 5

<h4>Introduction</h4>There have been a wide range of preclinical studies testing cellular therapies to repair the injured spinal cord, yet they remain a challenge to translate because of inconsistencies in efficacy, limited number of patients with acute/subacute SCI and the high costs of clinical trials. Area covered: This paper focusses on the therapeutic potential of neural precursor cells (NPCs) because they can provide the cellular components capable of promoting repair and enhancing functio ...[more]

PMID: 27927055

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Project description:BACKGROUND:Traumatic spinal cord injury (SCI) triggers a chain of events that is accompanied by an inflammatory reaction leading to necrotic cell death at the core of the injury site, which is restricted by astrogliosis and apoptotic cell death in the surrounding areas. Activation of nuclear factor-?B (NF-?B) signaling pathway has been shown to be associated with inflammatory response induced by SCI. Here, we elucidate the pattern of activation of NF-?B in the pathology of SCI in rats and investigate the effect of transplantation of spinal neural precursors (SPC-01) on its activity and related astrogliosis. METHODS:Using a rat compression model of SCI, we transplanted SPC-01 cells or injected saline into the lesion 7?days after SCI induction. Paraffin-embedded sections were used to assess p65 NF-?B nuclear translocation at days 1, 3, 7, 10, 14, and 28 and to determine levels of glial scaring, white and gray matter preservation, and cavity size at day 28 after SCI. Additionally, levels of p65 phosphorylated at Serine536 were determined 10, 14, and 28?days after SCI as well as levels of locally secreted TNF-?. RESULTS:We determined a bimodal activation pattern of canonical p65 NF-?B signaling pathway in the pathology of SCI with peaks at 3 and 28?days after injury induction. Transplantation of SCI-01 cells resulted in significant downregulation of TNF-? production at 10 and 14?days after SCI and in strong inhibition of p65 NF-?B activity at 28?days after SCI, mainly in the gray matter. Moreover, reduced formation of glial scar was found in SPC-01-transplanted rats along with enhanced gray matter preservation and reduced cavity size. CONCLUSIONS:The results of this study demonstrate strong immunomodulatory properties of SPC-01 cells based on inhibition of a major signaling pathway. Canonical NF-?B pathway activation underlines much of the immune response after SCI including cytokine, chemokine, and apoptosis-related factor production as well as immune cell activation and infiltration. Reduced inflammation may have led to observed tissue sparing. Additionally, such immune response modulation could have impacted astrocyte activation resulting in a reduced glial scar.

Dataset Information

Improving the therapeutic efficacy of neural progenitor cell transplantation following spinal cord injury.

Publications

Improving the therapeutic efficacy of neural progenitor cell transplantation following spinal cord injury.

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