Cell transplantation to repair the injured spinal cord

Hall, Adam A.; Fortino, Tara A.; Spruance, Victoria M.; Niceforo, Alessia; Phelps, Patricia E.; Priest, Catherine A.; Zholudeva, Lyandysha V.; Lane, Megan

doi:10.1016/bs.irn.2022.09.008

Cited by 4 publications

(5 citation statements)

References 477 publications

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“…Recent studies in regenerative medicine have strived to address these challenges by targeting the precise replacement of lost neurons and the restoration of the disrupted neural network. While cell transplantation remains a promising approach to address this neural repair (Fischer, Dulin et al 2020) (Hall, Fortino et al 2022), reprogramming methods offer a means of harnessing the existing host tissues to produce new populations of cells that are most needed for repair. These approaches include the direct reprogramming of non-neuronal cells into neurons (Gotz and Bocchi 2021).…”

Section: Discussionmentioning

confidence: 99%

Challenges and Efficacy of Astrocyte-to-Neuron Reprogramming in Spinal Cord Injury: In Vitro Insights and In Vivo Outcomes

Niceforo,

Zholudeva,

Fernandes

et al. 2024

Preprint

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Traumatic spinal cord injury (SCI) leads to the disruption of neural pathways, causing loss of neural cells, with subsequent reactive gliosis and tissue scarring that limit endogenous repair. One potential therapeutic strategy to address this is to target reactive scar-forming astrocytes with direct cellular reprogramming to convert them into neurons, by overexpression of neurogenic transcription factors. Here we used lentiviral constructs to overexpress Ascl1 or a combination of microRNAs (miRs) miR124, miR9/9*and NeuroD1 transfected into cultured and in vivo astrocytes. In vitro experiments revealed cortically-derived astrocytes display a higher efficiency (70%) of reprogramming to neurons than spinal cord-derived astrocytes. In a rat cervical SCI model, the same strategy induced only limited reprogramming of astrocytes. Delivery of reprogramming factors did not significantly affect patterns of breathing under baseline and hypoxic conditions, but significant differences in average diaphragm amplitude were seen in the reprogrammed groups during eupneic breathing, hypoxic, and hypercapnic challenges. These results show that while cellular reprogramming can be readily achieved in carefully controlled in vitro conditions, achieving a similar degree of successful reprogramming in vivo is challenging and may require additional steps.

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Section: Discussionmentioning

confidence: 99%

Challenges and Efficacy of Astrocyte-to-Neuron Reprogramming in Spinal Cord Injury: In Vitro Insights and In Vivo Outcomes

Niceforo,

Zholudeva,

Fernandes

et al. 2024

Preprint

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“…Neuronal transplantation can also be used to repair a damaged spinal cord, for example, by generating new circuits that can relay information from injured neurons rostral to the injury to deafferented neuron populations caudal to the injury [174,184]. Depending on the donor neuron type, they can also provide neurochemical inputs into damaged spinal networks to modulate activity.…”

Section: Cell Transplantationmentioning

confidence: 99%

“…An important consideration is that they can be derived from either the olfactory nasal mucosa or directly (more invasively) from the olfactory bulb. These two cell sources yield quite different cells that have unique properties [184]. Olfactory ecto-mesenchymal stem cells derived from the mucosa were transplanted into the cervical spinal cord to promote the repair of respiratory pathways and were reported to improve diaphragmatic and phrenic activity associated with reduced spinal inflammation 4 months after transplantation in an acute (2 days after SCI) model of C2 contusion in rats [191].…”

Section: Cell Transplantationmentioning

confidence: 99%

Therapeutic Strategies Targeting Respiratory Recovery after Spinal Cord Injury: From Preclinical Development to Clinical Translation

Michel‐Flutot

Lane

Lepore

et al. 2023

Cells

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High spinal cord injuries (SCIs) lead to permanent functional deficits, including respiratory dysfunction. Patients living with such conditions often rely on ventilatory assistance to survive, and even those that can be weaned continue to suffer life-threatening impairments. There is currently no treatment for SCI that is capable of providing complete recovery of diaphragm activity and respiratory function. The diaphragm is the main inspiratory muscle, and its activity is controlled by phrenic motoneurons (phMNs) located in the cervical (C3–C5) spinal cord. Preserving and/or restoring phMN activity following a high SCI is essential for achieving voluntary control of breathing. In this review, we will highlight (1) the current knowledge of inflammatory and spontaneous pro-regenerative processes occurring after SCI, (2) key therapeutics developed to date, and (3) how these can be harnessed to drive respiratory recovery following SCIs. These therapeutic approaches are typically first developed and tested in relevant preclinical models, with some of them having been translated into clinical studies. A better understanding of inflammatory and pro-regenerative processes, as well as how they can be therapeutically manipulated, will be the key to achieving optimal functional recovery following SCIs.

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“…Promising therapeutic approaches that are currently in development broadly target the protection of nervous system tissue from further damage or promote axon regeneration, plasticity, and repair, to either lessen functional loss or restore function, respectively. These approaches include (1) pharmacological therapies that target the processes of inflammation, cell death, gliosis, or abortive axon growth [3][4][5][6]; (2) transplantation of cells into the injured cord to replace lost tissue or act as a bridge for regeneration [7][8][9][10][11], including Schwann cells [12][13][14][15], olfactory ensheathing cells [16][17][18], mesenchymal stem cells [19,20], or induced pluripotent stem cells [21][22][23][24]; (3) gene therapy with viral-vector-mediated delivery of genes encoding factors that are neurotrophic or neuroprotective [25][26][27][28][29]; (4) biomaterials and synthetic scaffolds of polymers and gels that can bridge the gap between injured axons and their targets or which possess the capacity to deliver growth promoting molecules [30][31][32][33][34][35];…”

Section: Spinal Cord Injury and Promising Therapeutic Approaches For ...mentioning

confidence: 99%

Schwann Cell-Derived Exosomal Vesicles: A Promising Therapy for the Injured Spinal Cord

Ghosh,

Pearse

2023

IJMS

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Exosomes are nanoscale-sized membrane vesicles released by cells into their extracellular milieu. Within these nanovesicles reside a multitude of bioactive molecules, which orchestrate essential biological processes, including cell differentiation, proliferation, and survival, in the recipient cells. These bioactive properties of exosomes render them a promising choice for therapeutic use in the realm of tissue regeneration and repair. Exosomes possess notable positive attributes, including a high bioavailability, inherent safety, and stability, as well as the capacity to be functionalized so that drugs or biological agents can be encapsulated within them or to have their surface modified with ligands and receptors to imbue them with selective cell or tissue targeting. Remarkably, their small size and capacity for receptor-mediated transcytosis enable exosomes to cross the blood–brain barrier (BBB) and access the central nervous system (CNS). Unlike cell-based therapies, exosomes present fewer ethical constraints in their collection and direct use as a therapeutic approach in the human body. These advantageous qualities underscore the vast potential of exosomes as a treatment option for neurological injuries and diseases, setting them apart from other cell-based biological agents. Considering the therapeutic potential of exosomes, the current review seeks to specifically examine an area of investigation that encompasses the development of Schwann cell (SC)-derived exosomal vesicles (SCEVs) as an approach to spinal cord injury (SCI) protection and repair. SCs, the myelinating glia of the peripheral nervous system, have a long history of demonstrated benefit in repair of the injured spinal cord and peripheral nerves when transplanted, including their recent advancement to clinical investigations for feasibility and safety in humans. This review delves into the potential of utilizing SCEVs as a therapy for SCI, explores promising engineering strategies to customize SCEVs for specific actions, and examines how SCEVs may offer unique clinical advantages over SC transplantation for repair of the injured spinal cord.

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Cell transplantation to repair the injured spinal cord

Cited by 4 publications

References 477 publications

Challenges and Efficacy of Astrocyte-to-Neuron Reprogramming in Spinal Cord Injury: In Vitro Insights and In Vivo Outcomes

Challenges and Efficacy of Astrocyte-to-Neuron Reprogramming in Spinal Cord Injury: In Vitro Insights and In Vivo Outcomes

Therapeutic Strategies Targeting Respiratory Recovery after Spinal Cord Injury: From Preclinical Development to Clinical Translation

Schwann Cell-Derived Exosomal Vesicles: A Promising Therapy for the Injured Spinal Cord

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