Regenerative replacement of neural cells for treatment of spinal cord injury

McIntyre, William Brett; Pieczonka, Katarzyna; Khazaei, Mohamad; Fehlings, Michael G.

doi:10.1080/14712598.2021.1914582

Cited by 7 publications

(8 citation statements)

References 164 publications

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“…After SCI, many cells in the spinal cord are damaged, among which a large number of neuronal cells undergo programmed cell death and necrosis [ 37 ]. Neuronal cells, the main components of the CNS, not only transmit signals, but also secrete several neurotrophic factors and some chemical substances when stimulated by the outside world [ 38 ]. Spinal cord injury also stimulates the immune microenvironment, and various nerve cells in the CNS respond with immune responses to resist external interference [ 38 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…Neuronal cells, the main components of the CNS, not only transmit signals, but also secrete several neurotrophic factors and some chemical substances when stimulated by the outside world [ 38 ]. Spinal cord injury also stimulates the immune microenvironment, and various nerve cells in the CNS respond with immune responses to resist external interference [ 38 , 39 ]. Among them, neuroinflammatory and oxidative stress are essential [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

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Melatonin Attenuates Spinal Cord Injury in Mice by Activating the Nrf2/ARE Signaling Pathway to Inhibit the NLRP3 Inflammasome

Wang

Huang

et al. 2022

Cells

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Spinal cord injury (SCI) is a central nervous system (CNS) trauma involving inflammation and oxidative stress, which play important roles in this trauma’s pathogenesis. Therefore, controlling inflammation is an effective strategy for SCI treatment. As a hormone, melatonin is capable of producing antioxidation and anti-inflammation effects. In the meantime, it also causes a neuroprotective effect in various neurological diseases. Nrf2/ARE/NLRP3 is a well-known pathway in anti-inflammation and antioxidation, and Nrf2 can be positively regulated by melatonin. However, how melatonin regulates inflammation during SCI is poorly explored. Therefore, it was investigated in this study whether melatonin can inhibit the NLRP3 inflammasome through the Nrf2/ARE signaling pathway in a mouse SCI model. Methods: A model of SCI was established in C57BL/6 mice and PC12 cells. The motor function of mice was detected by performing an open field test, and Nissl staining and terminal deoxynucleotidyl transferase dUTP nick end labeling were carried out to evaluate the survival of neurons. Mitochondrial dysfunction was detected by transmission electron microscopy (TEM) and by assessing the mitochondrial membrane potential. In addition, the expression of NLRP3 inflammasome and oxidative-stress-related proteins were detected through Western blot and immunofluorescence double staining. Results: By inhibiting neuroinflammation and reducing neuronal death, melatonin promotes the recovery of neuromotor function. Besides this, melatonin is able to reduce the damage that causes neuronal mitochondrial dysfunction, reduce the level of reactive oxygen species (ROS) and malondialdehyde, and enhance the activity of superoxide dismutase and the production of glutathione peroxidase. Mechanically, melatonin inhibits the activation of NLRP3 inflammasomes and reduces the secretion of pro-inflammatory factors through the Nrf2/ARE signaling. Conclusions: In conclusion, melatonin inhibits the NLRP3 inflammasome through stimulation of the Nrf2/ARE pathway, thereby suppressing neuroinflammation, reducing mitochondrial dysfunction, and improving the recovery of nerve function after SCI.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Melatonin Attenuates Spinal Cord Injury in Mice by Activating the Nrf2/ARE Signaling Pathway to Inhibit the NLRP3 Inflammasome

Wang

Huang

et al. 2022

Cells

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“…Ultimately, these biasing methods can help to ensure that the final cell phenotypes match the circuit of interest in order to optimize NSPC integration. 15 , 72 …”

Section: Additional Considerationsmentioning

confidence: 99%

“…However, the specificity with which the NSPC-derived oligodendrocytes and neurons choose their targets and integrate within specific host neural networks remains unclear and introduces additional challenges. 14 , 15 Ensuring that the cell grafts migrate toward and integrate within the appropriate endogenous circuits is paramount to ensuring optimal functional recovery, as aberrant integration can lead to potential side effects. Moreover, the integration of the cells should align with the deficits and therapeutic goals of the patient.…”

Section: Introductionmentioning

confidence: 99%

Incorporating Combinatorial Approaches to Encourage Targeted Neural Stem/Progenitor Cell Integration Following Transplantation in Spinal Cord Injury

Pieczonka

Fehlings

2023

Stem Cells Translational Medicine

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Spinal cord injury (SCI) severely diminishes quality of life and presents patients with a substantial financial burden. The lack of a curative treatment has guided efforts toward identifying potential regenerative treatments. Neural stem/progenitor cell (NSPC) transplantation represents a promising strategy for the regeneration of the injured spinal cord due to the ability of these cells to replace neural cells lost post-injury. However, the transplant-derived oligodendrocytes and neurons need to be able to associate and integrate within the appropriate endogenous circuits to guarantee optimal functional recovery. To date, the integration of these transplant-derived cells has lacked specificity and remains a challenge. As such, it appears that the transplanted cells will require additional guidance cues to instruct the cells where to integrate. In the present review, we propose a variety of combinatorial techniques that can be used in conjunction with NSPC transplantation to direct the cells toward particular circuits of interest. We begin by introducing distinct molecular signatures that assist in the formation of specific circuits during development, and highlight how favorable molecular cues can be incorporated within the cells and their environment to guide the grafted cells. We also introduce alternative methods including task-specific rehabilitation, galvanotaxis, and magnet-based tools, which can be applied to direct the integration of the grafted cells toward the stimulated circuits. Future research examining these combinatorial efforts may serve to improve outcomes following SCI.

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“…NSCs can self-renew and play a role in neurogenesis in the adult brain [ 22 , 23 ]. NSCs preferentially differentiate into neural lineages such as neurons, astrocytes, and oligodendrocytes, which are attractive for clinical use in CNS diseases [ 24 ]. NSCs also secrete beneficial paracrine factors that can help regenerate the damaged CNSs [ 25 - 27 ].…”

Section: Basic Characteristic Of Stem Cellsmentioning

confidence: 99%

Advances in Neural Stem Cell Therapy for Spinal Cord Injury: Safety, Efficacy, and Future Perspectives

et al. 2022

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Spinal cord injury (SCI) is a devastating central nervous system (CNS) injury that leads to severe disabilities in motor and sensory functions, causing significant deterioration in patients' quality of life.Owing to the complexity of SCI pathophysiology, there has been no effective treatment for reversing neural tissue damage and recovering neurological functions. Several novel therapies targeting different stages of pathophysiological mechanisms of SCI have been developed. Among these, treatments using stem cells have great potential for the regeneration of damaged neural tissues. In this review, we have summarized recent preclinical and clinical studies focusing on neural stem cells (NSCs). NSCs are multipotent cells with specific differentiation capabilities for neural lineage. Several preclinical studies have demonstrated the regenerative effects of transplanted NSCs in SCI animal models through both paracrine effects and direct neuronal differentiation, restoring synaptic connectivity and neural networks. Based on the positive results of several preclinical studies, phase I and II clinical trials using NSCs have been performed. Despite several hurdles and issues that need to be addressed in the clinical use of NSCs in patients with SCI, gradual progress in the technical development and therapeutic efficacy of NSCs treatments has enhanced the prospects for cell-based treatments in SCI.

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Regenerative replacement of neural cells for treatment of spinal cord injury

Cited by 7 publications

References 164 publications

Melatonin Attenuates Spinal Cord Injury in Mice by Activating the Nrf2/ARE Signaling Pathway to Inhibit the NLRP3 Inflammasome

Melatonin Attenuates Spinal Cord Injury in Mice by Activating the Nrf2/ARE Signaling Pathway to Inhibit the NLRP3 Inflammasome

Incorporating Combinatorial Approaches to Encourage Targeted Neural Stem/Progenitor Cell Integration Following Transplantation in Spinal Cord Injury

Advances in Neural Stem Cell Therapy for Spinal Cord Injury: Safety, Efficacy, and Future Perspectives

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